Coexpression of CD25 and OX40 (CD134) Receptors Delineates Autoreactive T-cells in Type 1 Diabetes

Endl, Josef

doi:10.2337/diabetes.55.1.50

Cited by 19 publications

(31 citation statements)

References 27 publications

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“…1a). These results agree with recent reports that described coexpression of CD25 and CD134 after Ag stimulation of cloned CD4 ϩ T cells from PBMC in the settings of autoimmunity (27) or HIV infection (18) and single up-regulation of CD134 in recall responses to MTB Ags (28).…”

Section: Discussionsupporting

confidence: 82%

“…We are also investigating application of the CD25/CD134 assay for recall responses to Ags from common pathogens with low immunogenicity such as hepatitis C virus, and responses to autoantigens, as had been described for T cell clones associated with type 1 diabetes (27). Similarly, it may also be possible to study CD4 ϩ T cell responses to tumor Ags, particularly following the recently described efficacy of infusion with a melanoma-specific CD4 ϩ T cell clone (32).…”

Section: Cd134mentioning

confidence: 99%

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High Levels of Human Antigen-Specific CD4+ T Cells in Peripheral Blood Revealed by Stimulated Coexpression of CD25 and CD134 (OX40)

Zaunders

Munier

Seddiki

et al. 2009

The Journal of Immunology

157

209

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Ag-specific human CD4+ memory T lymphocytes have mostly been studied using assays of proliferation in vitro. Intracellular cytokine and ELISPOT assays quantify effector cell populations but barely detect responses to certain recall Ags that elicit strong proliferative responses, e.g., tetanus toxoid, that comprise non-Th1 CD4+ cells. We have found that culturing whole blood with Ag for 40–48 h induces specific CD4+ T cells to simultaneously express CD25 and CD134. This new technique readily detects responses to well-described CD4+ T cell recall Ags, including preparations of mycobacteria, CMV, HSV-1, influenza, tetanus toxoid, Candida albicans, and streptokinase, as well as HIV-1 peptides, with high specificity. The assay detects much higher levels of Ag-specific cells than intracellular cytokine assays, plus the cells retain viability and can be sorted for in vitro expansion. Furthermore, current in vitro assays for human CD4+ memory T lymphocytes are too labor-intensive and difficult to standardize for routine diagnostic laboratories, whereas the whole-blood CD25+CD134+ assay combines simplicity of setup with a straightforward cell surface flow cytometry readout. In addition to revealing the true extent of Ag-specific human CD4+ memory T lymphocytes, its greatest use will be as a simple in vitro monitor of CD4+ T cell responses to Ags such as tuberculosis infection or vaccines.

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Section: Discussionsupporting

confidence: 82%

Section: Cd134mentioning

confidence: 99%

High Levels of Human Antigen-Specific CD4+ T Cells in Peripheral Blood Revealed by Stimulated Coexpression of CD25 and CD134 (OX40)

Zaunders

Munier

Seddiki

et al. 2009

The Journal of Immunology

157

209

View full text Add to dashboard Cite

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“…Autoreactive CD4+ T cells in T1D display characteristics associated with prior antigen experience or chronic activation, including cell surface molecules CD45RO [11;12], Kv1.3 [13], and OX40 [14], and can be activated without co-stimulatory signals [15]. These maturation characteristics distinguish autoreactive cells in T1D subjects from similar, potentially autoreactive, naïve cells, which are present in normal individuals [11][12][13], and identify potential biomarkers that may correlate with clinical status.…”

Section: Discussionmentioning

confidence: 99%

Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation

Laughlin

Burke

Pugliese

et al. 2008

Clinical Immunology

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CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigenspecific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.

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“…These include proliferation to Ag in the absence of costimulatory signals (14) and the presence of specific late activation markers (15). These studies suggest that it may be possible to uniquely identify autoreactive T cell responses in at-risk subjects and patients using assays that selectively measure memory T cell responses.…”

Section: T Ype I Diabetes Mellitus (T1dm)mentioning

confidence: 99%

Evidence for In Vivo Primed and Expanded Autoreactive T Cells as a Specific Feature of Patients with Type 1 Diabetes

Monti

Scirpoli

Rigamonti

et al. 2007

The Journal of Immunology

113

125

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Identifying β cell autoantigen-reactive T cells that are involved in the pathogenesis of type 1 diabetes has been troublesome for many laboratories. Disease-relevant autoreactive T cells should be in vivo Ag experienced. The aim of this study was to test this hypothesis and then use this principle as a strategy for identifying diabetes-relevant autoreactive T cells. In this study, a CSFE dilution assay was used to detect glutamic acid decarboxylase 65 (GAD65)- and insulin-responsive T cells and HLA-0201*-GAD65114–122 pentamers were used to detect CD8+ GAD-responsive T cells in memory CD45RO+ and naive CD45RO− cell populations from patients with type 1 diabetes and healthy control subjects. T cell proliferative history was evaluated by flow cytometry telomere length measurement. CD4+ and CD8+ T cells specific for GAD65 and insulin were present in patients with type 1 diabetes and control subjects. Within the naive CD45RO− cells, CD4+ and CD8+ T cell responses were similar between patients and controls. Within the memory CD45RO+ cells, CD4+ T cell responses against whole GAD65 and insulin and HLA-0201*-GAD65114–122 pentamer-positive CD8+ T cells were found in patients with type 1 diabetes, but not in control subjects (p < 0.05 for all). Responding cells from the CD45RO+ T cell population had substantially shorter telomere lengths than responding cells from the CD45RO− cell population. Diabetes-specific autoreactive T cells in the circulation have uniquely undergone sustained in vivo proliferation and differentiation into memory T cells. Prior selection of these cells is possible and is a way to identify diabetes-relevant target Ags and epitopes.

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Coexpression of CD25 and OX40 (CD134) Receptors Delineates Autoreactive T-cells in Type 1 Diabetes

Abstract: T-cell-mediated loss of pancreatic

Cited by 19 publications

References 27 publications

High Levels of Human Antigen-Specific CD4+ T Cells in Peripheral Blood Revealed by Stimulated Coexpression of CD25 and CD134 (OX40)

High Levels of Human Antigen-Specific CD4+ T Cells in Peripheral Blood Revealed by Stimulated Coexpression of CD25 and CD134 (OX40)

Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation

Evidence for In Vivo Primed and Expanded Autoreactive T Cells as a Specific Feature of Patients with Type 1 Diabetes

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