ANTIGEN-PRESENTING CELLS IN ADOPTIVELY TRANSFERRED AND SPONTANEOUS AUTOIMMUNE DIABETES

被引:92
作者
LO, D
REILLY, CR
SCOTT, B
LIBLAU, R
MCDEVITT, HO
BURKLY, LC
机构
[1] STANFORD UNIV, MED CTR, SCH MED, DEPT MICROBIOL & IMMUNOL, STANFORD, CA 94305 USA
[2] BIOGEN, CAMBRIDGE, MA USA
关键词
DIABETES; AUTOIMMUNITY; TRANSGENIC MICE; ANTIGEN-PRESENTING CELLS;
D O I
10.1002/eji.1830230744
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Histological techniques were used to identify antigen-presenting cells (APC) in adoptively transferred diabetes in NOD mice and Ins-HA transgenic mice, and in spontaneously diabetic NOD mice. In adoptively transferred disease, CD4+ T cells and F4/80+ macrophages dominated early infiltrates. By contrast, in spontaneously developing diabetes in NOD mice, lymphocytic infiltrates appeared to be well organized around a network of VCAM-1+ NLDC-145+ ICAM-1+ dendritic cells. Thus, the primary APC spontaneous autoimmune disease appears to be the strongly stimulatory dendritic cell rather than the normally resident macrophage. Next, we used chimeric animals to demonstrate that insulitis and diabetes could occur even when responding T cells were unable to recognize islet-specific antigen directly on beta cells. Altogether, the results demonstrate that immune-mediated damage does not require direct contact between CD4+ T cells and beta cells. Moreover, despite the induction of ICAM-1, VCAM-1, and class II on vascular endothelium near islet infiltrates, these experiments show that recruitment of lymphocytes occurs even when antigen presentation is not possible on vascular endothelium.
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页码:1693 / 1698
页数:6
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