共 45 条
Amplification of Autoimmune Response through Induction of Dendiritic Cell Maturation in Inflamed Tissues
被引:59
作者:
Melli, Kristin
[1
]
Friedman, Rachel S.
[2
]
Martin, Ashley E.
[1
]
Finger, Erik B.
[1
]
Miao, Gang
[1
]
Szot, Gregory L.
[3
]
Krummel, Matthew F.
[2
]
Tang, Qizhi
[1
]
机构:
[1] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Univ Calif Diabet Ctr, Dept Med, San Francisco, CA 94143 USA
关键词:
GREEN FLUORESCENT PROTEIN;
NONOBESE DIABETIC MOUSE;
DENDRITIC CELLS;
T-CELLS;
IN-VIVO;
BETA-CELLS;
NOD MICE;
SELF-ANTIGENS;
LYMPH-NODE;
ISLETS;
D O I:
10.4049/jimmunol.0803543
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing beta cells in the islets of Langerhans in type 1 diabetes. in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed beta cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40(high) intra-islet DCs up-regulated CCR7, and a small number of CD40(high) DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes. The Journal of Immunology, 2009, 182: 2590-2600.
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页码:2590 / 2600
页数:11
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