Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes

Lawson, J. M., Tremble, J., Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462, Beyan, H., Leslie, R. D. G., Peakman, M. and Tree, T. I. M. 2008. Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes. Clinical and Experimental Immunology 154 (3) , pp. 353-359. 10.1111/j.1365-2249.2008.03810.x

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Abstract

Type I diabetes (T1D) is a T cell-mediated autoimmune disease characterized by loss of tolerance to islet autoantigens, leading to the destruction of insulin-producing beta cells. Peripheral tolerance to self is maintained in health through several regulatory mechanisms, including a population of CD4+CD25hi naturally occurring regulatory T cells (Tregs), defects in which could contribute to loss of self-tolerance in patients with T1D. We have reported previously that near to T1D onset, patients demonstrate a reduced level of suppression by CD4+CD25hi Tregs of autologous CD4+CD25- responder cells. Here we demonstrate that this defective regulation is also present in subjects with long-standing T1D (> 3 years duration; P = 0·009). No difference was observed in forkhead box P3 or CD127 expression on CD4+CD25hi T cells in patients with T1D that could account for this loss of suppression. Cross-over co-culture assays demonstrate a relative resistance to CD4+CD25hi Treg-mediated suppression within the CD4+CD25- T cells in all patients tested (P = 0·002),while there appears to be heterogeneity in the functional ability of CD4+CD25hi Tregs from patients. In conclusion, this work demonstrates that defective regulation is a feature of T1D regardless of disease duration and that an impaired ability of responder T cells to be suppressed contributes to this defect.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Uncontrolled Keywords:	autoimmunity, diabetes, immune regulation, regulatory T cells
Publisher:	Wiley-Blackwell
ISSN:	0009-9104
Last Modified:	20 Oct 2022 07:45
URI:	https://orca.cardiff.ac.uk/id/eprint/26285

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