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‣ The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

MICHAELSSON, Jakob; BARBOSA, Hugo Marcelo R.; JORDAN, Kimberley A.; CHAPMAN, Joan M.; BRUNIALTI, Milena K. C.; KLEINE NETO, Walter; NUKUI, Youko; SABINO, Ester C.; CHIEIA, Marco Antonio; OILIVEIRA, Acary Souza Bulle; NIXON, Douglas F.; KALLAS, Esper G.
Fonte: BIOMED CENTRAL LTD Publicador: BIOMED CENTRAL LTD
Tipo: Artigo de Revista Científica
Português
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Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation...

‣ The involvement of CD4(+)CD25(+) T cells in the acute phase of Trypanosoma cruzi infection

MARIANO, Flavia S.; GUTIERREZ, Fredy R. S.; PAVANELLI, Wander R.; MILANEZI, Cristiane M.; CAVASSANI, Karen A.; MOREIRA, Ana P.; FERREIRA, Beatriz R.; CUNHA, Fernando Q.; CARDOSO, Cristina R.; SILVA, Joao S.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
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The infection with Trypanosoma cruzi leads to a vigorous and apparently uncontrolled inflammatory response in the heart. Although the parasites trigger specific immune response, the infection is not completely cleared out, a phenomenon that in other parasitic infections has been attributed to CD4(+)CD25(+) T cells (Tregs). Then, we examined the role of natural Tregs and its signaling through CD25 and GITR in the resistance against infection with T. cruzi. Mice were treated with mAb against CD25 and GITR and the parasitemia, mortality and heart pathology analyzed. First, we demonstrated that CD4(+)CD25(+)GITR(+)Foxp3(+) T cells migrate to the heart of infected mice. The treatment with anti-CD25 or anti-GITR resulted in increased mortality of these infected animals. Moreover, the treatment with anti-GITR enhanced the myocarditis, with increased migration of CD4(+), CD8(+), and CCR5(+) leukocytes, TNF-alpha production, and tissue parasitism, although it did not change the systemic nitric oxide synthesis. These data showed a limited role for CD25 signaling in controlling the inflammatory response during this protozoan infection. Also, the data suggested that signaling through GITR is determinant to control of the heart inflammation, parasite replication...

‣ Identificação de marcadores moleculares para células T reguladoras humanas com perfil CD4+CD25+ por phage display; Peptide phage display for the identification of novel molecular markers on human thymic regulatory CD4+CD25+ T cells

Mundin, Georgia Sabio Porto
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 29/02/2008 Português
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Há dados na literatura indicando que as células que saem do timo com o fenótipo CD4+CD25+ são desenvolvidas continuamente como uma linhagem independente e possuem um papel importante no processo de regulação da resposta imune. Essas células são chamadas células T reguladoras naturais. Várias questões sobre estas células permanecem em aberto, como por exemplo, como elas são geradas, o que é determinante na sua atividade reguladora e que marcadores específicos podem ser usados para identificá-las? Dentro deste contexto, o nosso objetivo neste trabalho foi identificar no timo e em timócitos CD4+/CD25+ humanos, novas moléculas potencialmente importantes no desenvolvimento e/ou na atividade supressora das células T reguladoras naturais. Para este objetivo, utilizamos a abordagem de phage display, com uma biblioteca de fagos de peptídeos, e timos humanos obtidos de pacientes portadores de cardiopatias congênitas, submetidos a cirurgias cardíacas realizadas no InCor. A busca dessas moléculas foi feita, separadamente, em 3 tipos de material biológico: timócitos totais, fragmento do tecido tímico e timócitos CD4+/CD25+. Antes da incubação da biblioteca de fagos com os timócitos totais e timócitos CD4+/CD25+ (separação em FACS)...

‣ Evaluation of CD4+CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens

Braz,Suellen Carvalho de Moura; Lorena,Virginia Maria Barros de; Melo,Adriene Siqueira; Cavalcanti,Maria da Gloria Aureliano Melo; Gomes,Yara de Miranda
Fonte: Sociedade Brasileira de Medicina Tropical - SBMT Publicador: Sociedade Brasileira de Medicina Tropical - SBMT
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2013 Português
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Introduction CD4+CD25+ T lymphocytes have been implicated in the regulation of host inflammatory response against Trypanosoma cruzi, and may be involved in the clinical course of the disease. Methods Peripheral blood mononuclear cells from patients with chronic Chagas disease were cultured in the presence of T. cruzi recombinant antigens and assayed for lymphocytes at distinct time points. Results It was possible to differentiate clinical forms of chronic Chagas disease at days 3 and 5 according to presence of CD4+CD25+ T cells in cell cultures. Conclusions Longer periods of cell culture proved to be potentially valuable for prospective evaluations of CD4+CD25+ T lymphocytes in patients with chronic Chagas disease.

‣ Immunohistochemical evaluation of CD25+ cell expression in the progression of periodontal disease

Lins,Ruthinéia Diogénes Alves Uchoa; Alves,Pollianna Muniz; Godoy,Gustavo Pina; Silveira,Ericka Janine Dantas; Queiroz,Lélia Maria Guedes; Freitas,Roseana de Almeida
Fonte: Fundação Odontológica de Ribeirão Preto Publicador: Fundação Odontológica de Ribeirão Preto
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 Português
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It was assessed the immunohistochemical profile of CD25+ cells in cases of chronic gingivitis (CG) and chronic periodontitis (CP). Immunohistochemistry was carried out using streptoavidin-biotin complex and anti-CD25 antibody in 17 cases of CG and 25 cases of CP. Sixteen cases (94.1%) of CG were immunopositive. CD25 was focally expressed in 50% of the sample and diffusely expressed in 25%. The stained cells were localized not only beneath the epithelium, but also far from it. In relation to the cellular density quantification of CD25+ cells, score ++ was the most common. Concerning CP, all cases were immunopositive. CD25+ cells were expressed in focal or diffuse pattern either close or far from the epithelium. Diffuse distribution of positive cells throughout the connective tissue was seen in 60% of the cases and 32% showed focal or diffuse cellular pattern. Sixteen cases (64%) received score +++. It was identified that CD25+ cells are present in either a focal or a diffuse pattern in connective tissue. Significant differences in the density of cellular immunostaining between CG and CP were found. The greatest density was observed in CP cases, which suggests that the infiltrate of lymphocytes show a higher degree of cellular activation in periodontitis compared with gingivitis.

‣ Highly purified CD25− resting T cells cannot be infected de novo with HIV-1

Chou, Chin-Sheng; Ramilo, Octavio; Vitetta, Ellen S.
Fonte: The National Academy of Sciences of the USA Publicador: The National Academy of Sciences of the USA
Tipo: Artigo de Revista Científica
Publicado em 18/02/1997 Português
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Previous studies have demonstrated that the expression of CD25 can distinguish CD25− latently infected cells from CD25+ cells actively producing virus. Our studies were designed to characterize the nature and stability of the viral genome in CD25− quiescent HIV-1-infected cells and to determine whether these cells could be infected de novo with HIV-1. Our results show that: (i) When unfractionated peripheral blood mononuclear cells are first infected with HIV-1 and the CD25− cells then isolated, the latter contain only incomplete DNA transcripts and no full-length DNA or 2-LTR circles. Phytohemagglutinin activation of these CD25− cells results in the generation of full-length viral DNA and p24 production. (ii) When CD25− CD4+ cells are first purified from peripheral blood mononuclear cells and then incubated with HIV-1, viral DNA cannot be detected, suggesting that these purified cells cannot be infected. Furthermore, CD25− adherent cells do not facilitate the infection of CD4+ CD25− T cells when they were present at the time of incubation with HIV-1. Taken together, these studies suggest either that (i) the CD25− cells containing incomplete DNA transcripts are derived from infected-activated CD25+ cells, which subsequently become CD25− or (ii) the presence of CD25+ cells is required for the infection of CD25− cells in vitro.

‣ Foxp3+ CD25– CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion

Zelenay, Santiago; Lopes-Carvalho, Thiago; Caramalho, Iris; Moraes-Fontes, Maria Francisca; Rebelo, Manuel; Demengeot, Jocelyne
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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Expression of the IL-2 receptor α chain (CD25) by peripheral CD4 T cells follows cellular activation. However, CD25 expression by CD4 cells is widely used as a marker to identify regulatory T cells (TR), although cells with regulatory properties are also found in the CD4+CD25– subset. By using in vivo functional assays and Foxp3 expression as a faithful marker of TR differentiation, we have evaluated the requirements for CD25 expression by peripheral TR. We first show that in vivo depletion of CD25+ cells prevents the development of spontaneous encephalomyelitis in recombination-activating gene (RAG)-deficient anti-myelin basic protein T cell antigen receptor (TCR) transgenic mice, and allows disease induction in otherwise healthy RAG-competent transgenic mice. Similar treatment in normal thymectomized animals is followed by the fast recovery of a normal number of CD25+ TR. Consistently, Foxp3-expressing TR encompassed in the CD25– cell population convert to CD25+ after homeostatic expansion and are selectable by IL-2 in vitro. Surface expression of CD25 on TR is controlled by the activity of conventional CD4 cells and is fully labile because it can be lost and regained without affecting the functional potential of the cells. These findings reveal that Foxp3-expressing CD25– cells constitute a peripheral reservoir of differentiated TR...

‣ Preferential Feline Immunodeficiency Virus (FIV) Infection of CD4+ CD25+ T-Regulatory Cells Correlates both with Surface Expression of CXCR4 and Activation of FIV Long Terminal Repeat Binding Cellular Transcriptional Factors

Joshi, Anjali; Garg, Himanshu; Tompkins, Mary B.; Tompkins, Wayne A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2005 Português
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Previously, we have characterized feline CD4+ CD25+ T-regulatory (Treg) cells with regard to their immune regulatory properties and ability to support feline immunodeficiency virus (FIV) replication in vitro and in vivo. Our studies showed that while CD4+ CD25+ cells were capable of replicating FIV in the presence of interleukin-2 (IL-2) alone, CD4+ CD25− cells harbored a latent infection that required a strong mitogenic stimulus to activate virus replication. In the present study, we investigated the mechanisms governing the preferential replication of FIV in highly purified CD4+ CD25+ Treg cells compared to their CD4+ CD25− counterparts. Studies aimed at elucidating mechanisms regulating infection of these cells revealed that CD4+ CD25− cells were less susceptible to FIV binding and entry than CD4+ CD25+ cells, which correlated with increased surface expression of FIV coreceptor CXCR4. In addition, the number of CD4+ CD25+ cells that expressed the primary receptor CD134 was greater than for CD4+ CD25− cells. Although increased permissiveness to FIV infection of CD4+ CD25− cells following mitogenic stimulation correlated strongly with upregulation of surface CXCR4, it did not correlate with CD134 expression. Further, study of intracellular factors regulating FIV replication revealed that CD4+ CD25+ but not CD4+ CD25− T cells showed constitutive and IL-2-responsive transactivation of activating transcription factor...

‣ Novel 5-Flucytosine-Resistant Clade of Candida dubliniensis from Saudi Arabia and Egypt Identified by Cd25 Fingerprinting

Al Mosaid, Asmaa; Sullivan, Derek J.; Polacheck, Itzhack; Shaheen, Faisal A.; Soliman, Osama; Al Hedaithy, Saleh; Al Thawad, Sahar; Kabadaya, Motaz; Coleman, David C.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Publicado em /08/2005 Português
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DNA fingerprinting of Candida dubliniensis isolates using the species-specific probe Cd25 previously showed that this species consists of two distinct groups, termed Cd25 group I and Cd25 group II. The present study investigated the population structure of 30 C. dubliniensis oral isolates from Saudi Arabia and Egypt using Cd25 fingerprinting and rRNA gene internal transcribed spacer region-based genotyping. Cd25 fingerprinting analysis of these isolates revealed two distinct populations, the first of which consisted of 10 closely related genotype 1 isolates (average similarity coefficient [SAB] value, 0.86). The second population of 20 isolates was much more heterogeneous (average SAB value, 0.35) and consisted of two distinct subpopulations, one of which consisted of genotype 3 isolates (n = 13) and the other of genotype 4 isolates (n = 7). A mixed dendrogram generated from the fingerprint data from the 30 Saudi Arabian and Egyptian isolates, 5 Israeli isolates, and 51 previously characterized international isolates (32 of Cd25 group I and 19 of Cd25 group II) revealed the presence of three distinct main clades. The first corresponded to the previously described Cd25 group I and contained all the Saudi Arabian, Egyptian, and Israeli genotype 1 isolates mixed with international isolates. The second clade corresponded to the previously described Cd25 group II and contained three Israeli isolates...

‣ CD4+CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses

Wing, Kajsa; Larsson, Pia; Sandström, Kerstin; Lundin, Samuel B; Suri-Payer, Elisabeth; Rudin, Anna
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /08/2005 Português
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Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25− thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-γ production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA− cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion...

‣ Phenotypic and functional characterization of human CD25+ B cells

Brisslert, Mikael; Bokarewa, Maria; Larsson, Pia; Wing, Kajsa; Collins, L Vincent; Tarkowski, Andrej
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/2006 Português
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We demonstrate that humans have a phenotypically and functionally distinct subset of B lymphocytes that express the interleukin (IL)-2 receptor (IL-2R) α-chain, cluster of differentiation (CD) 25. We found that one-third of the circulating CD20+ B cells expressed CD25 and, using fluorescence-activated cell sorter (FACS) analysis, that these cells were significantly larger and more granulated than B cells not expressing CD25. The simultaneous expression of the other two subunits (CD122 and CD132) and the proliferative responses of cells expressing CD25 to IL-2 suggested that, in addition to CD25, functional IL-2 receptors were expressed on this cell population. CD25 expression on B cells was selectively up-regulated by Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligands but not by a TLR3 ligand or Epstein–Barr virus (EBV) stimulation. Blockade of the nuclear factor (NF)-κB pathway completely abolished CD25 up-regulation by these B cells. Interestingly, CD25+ B cells expressed significantly higher levels of surface immunoglobulins but lacked the ability to secrete immunoglobulin (Ig), as compared with CD25− B cells. Furthermore, CD25+ B cells performed significantly better as antigen-presenting cells in allogeneic mixed lymphocyte reactions (MLR)...

‣ Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood

Wing, Kajsa; Ekmark, Ann; Karlsson, Helen; Rudin, Anna; Suri-Payer, Elisabeth
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /06/2002 Português
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CD4+ CD25+ regulatory T cells prevent organ-specific autoimmune diseases in various animal models. We analysed human lymphoid tissues to identify similar CD25+ regulatory T cells. Adult peripheral blood contained two populations of CD4+ T cells that expressed CD25 at different densities. The larger population (≈ 40%) expressed intermediate levels of CD25 (CD25+) and displayed a memory T-cell phenotype (CD45RA−/RO+, CD45RBlow, CD95+, CD62Llow, CD38low). The smaller population of cells (≈ 2%) expressed very high levels of CD25 (CD25++). In addition to the activation/memory T-cell antigens mentioned above they also expressed intracellular CD152 (CTLA-4) as well as enhanced levels of cell-surface CD122, similar to the murine CD4+ CD25+ regulatory counterpart. To exclude that the CD25++ cells had not been recently primed by external antigen we analysed cord blood and thymus. CD25++, CD152+ and CD122++ cells were present in paediatric thymus (10% of CD4+ CD8− thymocytes) expressing signs of recent selection (CD69+) and in cord blood (5% of CD4+ cells) where they showed a naive phenotype. In addition, cord blood contained a small population of CD25+ cells (≈ 2% of CD4 T cells) that were CD152− and CD122low and displayed signs of activation. Together with published data that CD25+ CD25++ cells from the thymus and peripheral blood are regulatory...

‣ Direct Expansion of Functional CD25+ CD4+ Regulatory T Cells by Antigen-processing Dendritic Cells

Yamazaki, Sayuri; Iyoda, Tomonori; Tarbell, Kristin; Olson, Kara; Velinzon, Klara; Inaba, Kayo; Steinman, Ralph M.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 21/07/2003 Português
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An important pathway for immune tolerance is provided by thymic-derived CD25+ CD4+ T cells that suppress other CD25− autoimmune disease–inducing T cells. The antigen-presenting cell (APC) requirements for the control of CD25+ CD4+ suppressor T cells remain to be identified, hampering their study in experimental and clinical situations. CD25+ CD4+ T cells are classically anergic, unable to proliferate in response to mitogenic antibodies to the T cell receptor complex. We now find that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs. With high doses of DCs in culture, CD25+ CD4+ and CD25− CD4+ populations initially proliferate to a comparable extent. With current methods, one third of the antigen-reactive T cell receptor transgenic T cells enter into cycle for an average of three divisions in 3 d. The expansion of CD25+ CD4+ T cells stops by day 5, in the absence or presence of exogenous interleukin (IL)-2, whereas CD25− CD4+ T cells continue to grow. CD25+ CD4+ T cell growth requires DC–T cell contact and is partially dependent upon the production of small amounts of IL-2 by the T cells and B7 costimulation by the DCs. After antigen-specific expansion...

‣ Conversion of CD4+ CD25− cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus

Liang, Shuang; Alard, Pascale; Zhao, Yuan; Parnell, Sarah; Clark, Sherry L.; Kosiewicz, Michele M.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 03/01/2005 Português
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The CD4+ CD25+ regulatory T cells play a critical role in controlling autoimmunity, but little is known about their development and maintenance. In this study, we investigated whether CD4+ CD25− cells can convert to CD4+ CD25+ regulatory T cells in vivo under natural conditions. CD4+ CD25− cells from CD45.1+ mice were sorted and transferred into congenic CD45.2+ mice. Converted CD4+ CD25+ cells could be detected in lymphoid organs as early as 1 wk after transfer and by 6 wk after transfer, 5–12% of transferred CD4+ cells expressed CD25. Converted CD4+ CD25+ cells themselves failed to proliferate after stimulation, but could suppress proliferation of responder cells in vitro, and also expressed high levels of Foxp3 mRNA. In addition, CD4+ CD25− cells transferred into thymectomized congenic mice converted to CD4+ CD25+ cells that also suppressed responder cell proliferation in vitro, and expressed high levels of Foxp3 mRNA. Finally, CD4+ CD25− cells transferred into B7−/− mice failed to convert into CD4+ CD25+ cells that exhibit the regulatory phenotype. These data indicate that CD4+ CD25− cells convert into CD4+ CD25+ regulatory T cells spontaneously in vivo and suggest that this conversion process could contribute significantly to the maintenance of the peripheral CD4+ CD25+ regulatory T cell population.

‣ Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice

Couper, Kevin N.; Blount, Daniel G.; de Souza, J. Brian; Suffia, Isabelle; Belkaid, Yasmine; Riley, Eleanor M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/04/2007 Português
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Investigation of the role of regulatory T cells (Treg) in model systems is facilitated by their depletion using anti-CD25 antibodies, but there has been considerable debate about the effectiveness of this strategy. Here, we have compared the depletion and repopulation of CD4+CD25+Foxp3+ Treg in uninfected and malaria-infected mice using 7D4 and/or PC61 anti-CD25 antibodies. We find that numbers and percentages of CD25hi cells, but not Foxp3+ cells, are transiently reduced after 7D4 treatment whereas treatment with PC61 - alone or in combination with 7D4 (7D4+PC61) - reduces, but does not eliminate, Foxp3+ cells for up to two weeks. Importantly, all protocols fail to eliminate significant populations of CD25-Foxp3+ or CD25lowFoxp3+ cells, which retain potent regulatory capacity. By adoptive transfer we show that repopulation of the spleen by CD25hiFoxp3+ cells results from re-expression of CD25 on peripheral populations of CD25-Foxp3+ but not from conversion of peripheral Foxp3- cells. CD25hiFoxp3+ repopulation occurs more rapidly in 7D4-treated mice than in 7D4+PC61-treated mice, reflecting ongoing clearance of emergent CD25+Foxp3+ cells by persistent PC61 antibody. However, in 7D4+PC61-treated mice undergoing acute malaria infection...

‣ Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes

Zhen, Yu; Sun, Lina; Liu, He; Duan, Kaizhong; Zeng, Chun; Zhang, Lianjun; Jin, Di; Peng, Jianxia; Ding, Wenjun; Zhao, Yong
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients. CD4+CD25+ T regulatory cells (Tregs) play pivotal roles in controlling immune homeostasis, immunity and tolerance. The effect of hyperglycemia on CD4+CD25+ Tregs has not yet been addressed. Here we used streptozotocin (STZ)-induced diabetic mice to study the effects of long-term hyperglycemia on CD4+CD25+ Tregs in vivo. Four months after the onset of diabetes, the frequency of CD4+CD25+Foxp3+ T regulatory cells was significantly elevated in the spleen, peripheral blood lymphocytes (PBLs), peripheral lymph nodes (pLNs) and mesenteric LNs (mLNs). CD4+CD25+ Tregs obtained from mice with diabetes displayed defective immunosuppressive functions and an activated/memory phenotype. Insulin administration rescued these changes in the CD4+CD25+ Tregs of diabetic mice. The percentage of thymic CD4+CD25+ naturally occurring Tregs (nTregs) and peripheral CD4+Helios+Foxp3+ nTregs were markedly enhanced in diabetic mice, indicating that thymic output contributed to the increased frequency of peripheral CD4+CD25+ Tregs in diabetic mice. In an in vitro assay in which Tregs were induced from CD4+CD25− T cells by transforming growth factor (TGF)-β...

‣ Control of CD4+ T Cell Function by CD4+CD25+ Regulatory T Cells

Sojka, Dorothy Katherine ; Fowell, Deborah
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
Português
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Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Microbiology and Immunology, 2009.; In the periphery thymus derived, naturally occurring CD4+CD25+Foxp3+ (Treg(s)) have the potential to suppress an extensive array of immune responses that exceed their original identification of preventing autoimmune disease. In recent years Treg mediated beneficial and harmful suppressive activities have been attributed to limiting responses to infectious agents and tumor antigens, respectively. In various immune settings Tregs have been implicated in controlling initial T cell activation, proliferation, differentiation, effector function, and migration. Although Tregs have an extensive suppressive agenda, their mechanisms of action are not well understood. Costimulatory signals from CD28 and CTLA-4 have been identified to regulate both target T cells and Tregs and can either help the cell escape suppression or mediate the suppression. This thesis will focus on the CD4+ effector functions that are modified by Tregs in the presence of CD28 signaling as well as the role of CTLA-4 in Treg function. To get a better understanding of Treg action we first investigated the kinetics of murine Treg activity in vitro. Tregs were suppressive within a surprisingly narrow kinetic window: necessary and sufficient only in the first 6-10h of culture. Importantly...

‣ Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation

Pino-lagos, Karina; Michea, Paula; Sauma, Daniela; Alba, Andrea; Morales, Jorge; Bono, María Rosa; Fierro, Alberto; Rosemblatt, Mario
Fonte: Sociedad de Biología de Chile Publicador: Sociedad de Biología de Chile
Tipo: Artigo de Revista Científica
Português
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http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602010000300010&lng=es&nrm=iso; One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (TREG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect TREG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled TREG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of TREG cells from 72 to 47%. Further inhibition to a 24% of TREG proliferation was obtained as a direct effect of CsA on TREG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.

‣ CD25+ T cells induce H. pylori-specific CD25- T cell anergy but are not required to maintain persistent hyporesponsiveness

Stuller, Kathleen A.; Ding, Hua; Redline, Raymond W.; Czinn, Steven J.; Blanchard, Thomas G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2008 Português
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The gastric pathogen Helicobacter pylori (H. pylori) infects over half the world's population. The lifelong infection induces gastric inflammation but the host fails to generate protective immunity. To study the lack of protective H. pylori immunity, CD4+CD25+ Treg cells were investigated for their ability to down-regulate H. pylori-specific CD4+CD25- cells in a murine model. CD25- lymphocytes from infected mice were hyporesponsive to antigenic stimulation in vitro even in the absence of CD25+ Treg cells unless treated with high dose IL-2. Transfer of CD45RBhi naïve CD25- cells from infected mice into rag1-/- mice challenged with H. pylori resulted in severe gastritis and reduced bacterial loads, whereas transfer of CD45RBlo memory CD25- cells from H. pylori-infected mice resulted in only mild gastritis and persistent infection. CD25- cells stimulated in the absence of CD25+ cells in rag1-/- mice promoted bacterial clearance, but lost this ability when subsequently transferred to wild type mice harboring CD25+ cells. These results demonstrate that CD25+ cells induce anergy in CD25- cells in response to H. pylori infection but are not required to maintain hyporesponsiveness. In addition, CD25+ cells are able to suppress previously activated CD25- cells when responding to H. pylori challenge in vivo.

‣ Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4(+)CD25(+) regulatory T cell proliferation

Bono Merino, María Rosa; Fierro, Alberto; Alba, Andrea; Rosemblatt, Mario; Morales, Jorge; Sauma, Daniela; Michea, Paula; Pino, Karina
Fonte: SOC BIOLGIA CHILE Publicador: SOC BIOLGIA CHILE
Tipo: Artículo de revista
Português
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Artículo de publicación ISI; One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (TREG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect TREG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled TREG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of TREG cells from 72 to 47%. Further inhibition to a 24% of TREG proliferation was obtained as a direct effect of CsA on TREG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.; This work was supported by grants from FONDECYT 1100448 (to MR)...