期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 154, 期 3, 页码 353-359出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2249.2008.03810.x
关键词
autoimmunity; diabetes; immune regulation; regulatory T cells
类别
资金
- Diabetes UK BDA [RD03/0002727]
- BDA [RD04/0002877]
- National Institute for Health Research
- St Thomas' National Health Service Foundation Trust
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(+)CD25(hi) naturally occurring regulatory T cells (T(regs)), 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(+)CD25(hi) T(regs) 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(+)CD25(hi) 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(+)CD25(hi) T(reg)-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(+)CD25(hi) T(regs) 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.
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