Injury- and Antigen-Specific Control of CD4 T Cell Reactivity by CD4+CD25+ Regulatory T Cells (88.42)

Abstract Severe injury augments the potency of CD4+CD25+ regulatory T cells (Tregs) suggesting that Tregs might play a role in controlling unwanted CD4 T cell responses in the injured host. To test whether enhanced Treg activity might occur by an antigen driven process, we compared T cell responses in Treg-depleted sham and burn mice that received unsorted or CD25-depleted CD4+ T-cells from DO-11.10 T cell receptor (TCR) transgenic mouse. Unsorted DO-11.10 CD4+ T cells contain 10% CD25+FoxP3+ T-cells. Treg-depleted or control mice received 5 x 106 CD4 T cells or CD25-depleted CD4 T cells by i.v. injection, were immunized OVA323-339 peptide and then underwent sham or burn injury under anesthesia. At day 7, lymph node and spleen cells were prepared and stained with DO-11.10 TCR specific antibody. We observed a significant increase in DO-11.10 T cell expansion in sham and burn Treg-depleted mice that received CD4+CD25− T cells. This increased expansion occurred in sham, but not burn mice, receiving unsorted CD4 T cells suggesting that the co-transfer of CD25+ DO-11.10 T cells was sufficient to suppress T cell expansion in injured mice. The results of CFSE-studies confirmed that antigen-stimulated CD4+CD25− T-cells proliferate more vigorously in burn as compared to sham mice, but that transferring unsorted T cells prevents the injury-induced CD4 T cell expansion. These results indicate that injury influences Treg activity in an antigen-specific fashion and suggest that Tregs may play an active role in modulating CD4 T cell reactivity following injury