RESEARCH - Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues

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J Immunol. 2009 Mar 1;182(5):2590-600.

Amplification of autoimmune response through induction of dendritic

cell maturation in inflamed tissues

Melli K, Friedman RS, AE, Finger EB, Miao G, Szot GL, Krummel MF, Tang Q.

Department of Surgery, University of California, San Francisco, CA 94143, USA.

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 this study, we investigated T cell induction of

intra-islet DC maturation during the progression of the disease 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.

PMID: 19234153

http://www.ncbi.nlm.nih.gov/pubmed/19234153

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