Regulatory CD8+CD28− T cells in heart transplant recipients

Colovai, Adriana I.; Mirza, Mansoor Raza; Vlad, George; Wang, S.u; Ho, Eric K.; Cortesini, Raffaello; Suciu‐Foca, Nicole

doi:10.1016/s0198-8859(02)00742-5

Cited by 104 publications

(90 citation statements)

References 19 publications

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“…In contrast, CD16 − CD56 ++ natural killer (NK)-cells were only seen in the PIL, whereas the majority of + T cells was observed in 38% of the PIL compared with 70% of the PBMC. In conclusion, a large population of CD8 + PIL T cells lacked expression of CD28, which is consistent with a phenotype of donor-specific regulatory T cells [10,16].…”

Section: Phenotyping Of Pil and Pbmcsupporting

confidence: 77%

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Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient

et al. 2008

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Aims/hypothesis Simultaneous kidney-pancreas transplantation is an established treatment for patients with type 1 diabetes and end-stage renal failure, even though restored beta cell function may become affected by recurrent islet autoimmunity or graft rejection. We characterised infiltrating lymphocytes isolated from a pancreatic graft with normal endocrine function in a kidney-pancreas recipient with type 1 diabetes. Methods The pancreas graft was removed due to recurrent graft pancreatitis of unknown cause. Pancreas-infiltrating lymphocytes and peripheral blood mononuclear cells (PBMC) were isolated and characterised phenotypically and functionally.Results Compared with PBMC, pancreas-infiltrating lymphocytes exhibited a distinct activation/memory phenotype and T cell receptor profile that were indicative of selective infiltration of the pancreas. Islet autoreactive CD8 + T cells could be detected in the pancreas and were increased in frequency compared with PBMC. Additionally, an augmentation of CD8 + CD28 − regulatory T cells was observed in the pancreas; these induced expression of the inhibitory receptor immunoglobulin-like transcript-3 on antigen-presenting cells in a donor HLA class I-specific manner. Conclusions/interpretation These data demonstrate the simultaneous presence of regulatory and effector T cells in the pancreas allograft of a recipient with type 1 diabetes. They also indicate that circulating islet autoreactive T cells may reflect immunological processes in pancreatic tissue, even though their frequency in the periphery may lead to underestimation of their presence in the pancreas. Additional specificities were also present in the pancreas that were undetectable in the circulation.Keywords Effector T cells . Pancreas transplantation . Regulatory T cells . Type 1 diabetesAbbreviations APC antigen presenting cell CCR7 chemokine (C-C motif) receptor 7 CDR3 complementarity-determining region 3 IMDM Iscove's Modified Dulbecco's Medium IGRP islet-specific glucose-6-phosphatase catalytic subunit-related protein ILT immunoglobulin-like transcript mAbs monoclonal antibodies MACS magnetic-activated cell-sorting Diabetologia (2009) 52:494-503

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Section: Phenotyping Of Pil and Pbmcsupporting

confidence: 77%

“…Of these regulatory T cells, CD8 + CD28 − Tsuppressor cells have been shown to be important in clinical solid organ transplantation [10,11]. However, these studies were focused on circulating cells while cells residing within the transplanted organ may be better indicators of the immunological response after allogeneic transplantation.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient

et al. 2008

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“…[48][49][50] Studies on the aging immune system have found that the number of CD8 þ CD28 À T cells increases with age and that these cells are resistant to apoptosis, having increased bcl-2 expression and decreased caspase 3 expression. [51][52][53] In addition, CD8 þ CD28 À T cells have been reported to have regulatory functions; CD8 þ CD28 À T cells have been implicated in tolerance in studies of cardiac transplant recipients, 54 in decreased antibody production following immunization in elderly patients 55 and tumor susceptibility and growth in cancer patients. 56,57 The downregulation of CD28 following tolerization might also explain the anti apoptotic effect of pCons treatment.…”

Section: Discussionmentioning

confidence: 99%

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

et al. 2010

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Tolerizing mice polygenically predisposed to lupus-like disease (NZB/NZW F1 females) with a peptide mimicking anti-DNA IgG sequences containing MHC class I and class II T cell determinants (pConsensus, pCons) results in protection from full-blown disease attributable in part to the induction of CD4 þ CD25 þ Foxp3 þ and CD8 þ Foxp3 þ regulatory T cells. We compared 45 000 murine genes in total white blood cells (WBC), CD4 þ T cells, and CD8 þ T cells from splenocytes of (NZBxNZW) F1 lupus-prone mice tolerized with pCons vs untreated naïve mice and found two-fold or greater differential expression for 448 WBC, 174 CD4, and 60 CD8 genes. We identified differentially expressed genes that played roles in the immune response and apoptosis. Using real-time PCR, we validated differential expression of selected genes (IFI202B, Bcl2, Foxp3, Trp-53, CCR7 and IFNar1) in the CD8 þ T cell microarray and determined expression of selected highly upregulated genes in different immune cell subsets. We also determined Smads expression in different immune cell subsets, including CD4 þ T cells and CD8 þ T cells, to detect the effects of TGF-b, known to be the major cytokine that accounts for the suppressive capacity of CD8 þ Treg in this system. Silencing of anti-apoptotic gene Bcl2 or interferon genes (IFI202b and IFNar1 in combination) in CD8 þ T cells from tolerized mice did not affect the expression of the other selected genes. However, silencing of Foxp3 reduced expression of Foxp3, Ifi202b and PD1-all of which are involved in the suppressive capacity of CD8 þ Treg in this model.

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“…The CD4+ CD25+ population can be divided into two different levels of expression, i.e. low CD25 level (defined CD4+ CD25low) and high CD25 level (defined CD4+ CD25bright) [9][10][11][12][13] that appear to have a tail to the right of the major population containing both CD4+ CD25low and CD4+ CD25-cells. FOXP3 expression was analysed using mononuclear cells purified from peripheral blood using Lymphoprep (1.077 g mL; AxisShield, Oslo, Norway) density gradient centrifugation.…”

Section: Patientsmentioning

confidence: 99%

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

et al. 2012

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Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by autoantibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28-cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25bright-FOXP3 and CD8+ CD28-circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age-and sex-matched healthy controls (HC, n = 30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25bright-FOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p = 0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3-''activated'' T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28-subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.

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Regulatory CD8+CD28− T cells in heart transplant recipients

Cited by 104 publications

References 19 publications

Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient

Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

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