T Cell Islet Accumulation in Type 1 Diabetes Is a Tightly Regulated, Cell-Autonomous Event

被引:116
作者
Lennon, Greig P. [1 ]
Bettini, Maria [1 ]
Burton, Amanda R. [1 ]
Vincent, Erica [1 ]
Arnold, Paula Y. [1 ]
Santamaria, Pere [2 ,3 ]
Vignali, Dario A. A. [1 ]
机构
[1] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Univ Calgary, Julia McFarlane Diabet Res Ctr, Calgary, AB T2N 4N1, Canada
[3] Univ Calgary, Dept Microbiol & Infect Dis, Inst Inflammat Infect & Immun, Fac Med, Calgary, AB T2N 4N1, Canada
基金
加拿大健康研究院;
关键词
RECEPTOR RETROGENIC MICE; MHC CLASS-I; INSULITIS; PEPTIDE; CLONES; MOUSE; AUTOIMMUNITY; INFLAMMATION; RECRUITMENT; EXPRESSION;
D O I
10.1016/j.immuni.2009.07.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Type 1 diabetes is a T cell-mediated autoimmune disease, characterized by lymphocytic infiltration of the pancreatic islets. It is currently thought that islet antigen specificity is not a requirement for islet entry and that diabetogenic T cells can recruit a heterogeneous bystander T cell population. We tested this assumption directly by generating T cell receptor (TCR) retrogenic mice expressing two different T cell populations. By combining diabetogenic and nondiabetogenic or nonautoantigen-specific T cells, we demonstrate that by stander T cells cannot accumulate in the pancreatic islets. Autoantigen-specific T cells that accumulate in islets, but do not cause diabetes, were also unaffected by the presence of diabetogenic T cells. Additionally, 67% of TCRs cloned from nonobese diabetic (NOD) islet-infiltrating CD4(+) T cells were able to mediate cell-autonomous islet infiltration and/or diabetes when expressed in retrogenic mice. Therefore, islet entry and accumulation appears to be a cell-autonomous and tightly regulated event and is governed by islet antigen specificity.
引用
收藏
页码:643 / 653
页数:11
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