Autoreactive Effector/Memory CD4(+) and CD8(+) T Cells Infiltrating Grafted and Endogenous Islets in Diabetic NOD Mice Exhibit Similar T Cell Receptor Usage

作者：Diz Ramiro; Garland Alaina; Vincent Benjamin G; Johnson Mark C; Spidale Nicholas; Wang Bo; Tisch Roland^*

来源：PLos One, 2012, 7(12): e52054.

DOI：10.1371/journal.pone.0052054

Islet transplantation provides a "cure'' for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by beta cell-specific CD4(+) and CD8(+) T cells. Insight into the T cell receptor (TCR) repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable beta (V beta) chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naive CD4(+) and CD8(+) T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+) T cell repertoire in the islet graft was dominated by one to four TCR V beta chains, and specific TCR V beta chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+) T cells expressed a limited number of prevalent TCR V beta chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+) T cells. Strikingly, the majority of NOD recipients showed an increase in TCR V beta 12-bearing effector/memory CD4(+) T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR V beta usage by effector/memory CD4(+) and CD8(+) T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+) and CD8(+) T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR V beta chain usage, and are similar to T cells that drive destruction of the endogenous islets. Citation: Diz R, Garland A, Vincent BG, Johnson MC, Spidale N, et al. (2012) Autoreactive Effector/Memory CD4(+) and CD8(+) T Cells Infiltrating Grafted and Endogenous Islets in Diabetic NOD Mice Exhibit Similar T Cell Receptor Usage. PLoS ONE 7(12): e52054. doi:10.1371/journal.pone.0052054

• 出版日期2012-12-14