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题名:Thymic Development of Autoreactive T Cells in NOD Mice Is Regulated in an Age-Dependent Manner.
作者:HE Q; MORILLON YM 2ND; SPIDALE NA; KROGER CJ; LIU B; SARTOR RB; WANG B; TISCH R;
来源:J Immunol. 2013 Nov 6. [ IF= 0.00 ] ]
URL :10.4049/jimmunol.1302273
日期:20131203
摘要:Inefficient thymic negative selection of self-specific T cells is associated with
several autoimmune diseases, including type 1 diabetes. The factors that
influence the efficacy of thymic negative selection, as well as the kinetics of
thymic output of autoreactive T cells remain ill-defined. We investigated thymic
production of beta cell-specific T cells using a thymus-transplantation model.
Thymi from different aged NOD mice, representing distinct stages of type 1
diabetes, were implanted into NOD.scid recipients, and the diabetogenicity of the
resulting T cell pool was examined. Strikingly, the development of
diabetes-inducing beta cell-specific CD4+ and CD8+ T cells was regulated in an
age-dependent manner. NOD.scid recipients of newborn NOD thymi developed
diabetes. However, recipients of thymi from 7- and 10-d-old NOD donor mice
remained diabetes-free and exhibited a progressive decline in islet infiltration
and beta cell-specific CD4+ and CD8+ T cells. A similar temporal decrease in
autoimmune infiltration was detected in some, but not all, tissues of recipient
mice implanted with thymi from NOD mice lacking expression of the autoimmune
regulator transcription factor, which develop multiorgan T cell-mediated
autoimmunity. In contrast, recipients of 10 d or older thymi lacked diabetogenic
T cells but developed severe colitis marked by increased effector T cells
reactive to intestinal microbiota. These results demonstrate that thymic
development of autoreactive T cells is limited to a narrow time window and occurs
in a reciprocal manner compared with colonic microbiota-responsive T cells in NOD
mice.

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