@entity3446 generates graft-homing XXXX suppressor CD8(+) T cells that confer donor-specific graft protection.

@entity8022 @entity2047 @entity19 @entity1618 @entity3446 @entity10867 @entity1961 @entity5350 @entity1349
It has been reported that @entity3446 (RPM) can induce de novo conversion of the conventional @entity1961 (+)Foxp3(-) T cells into @entity1961 (+)Foxp3(+) regulatory T cells (iTregs) in transplantation setting. It is not clear whether RPM can similarly generate suppressor CD8(+) T cells to facilitate graft acceptance. In this study, we investigated the ability of short-term RPM treatment in promoting long-term acceptance (LTA) of MHC-mismatched skin allografts by generating a CD8(+) suppressor T-cell population. We found that @entity1961 knockout (KO) @entity19 (in C57BL/6 background, H-2(b)) can promptly reject DBA/2 ( @entity8022 ) skin allografts with @entity1349 ( @entity1349 ) being 13 days (p < 0.01). However, a short course RPM treatment in these animals induced LTA with graft @entity1349 longer than 100 days. Adoptive transfer of CD8(+) T cells from LTA group into @entity5350 ( @entity5350 )-deficient @entity19 provided donor-specific protection of DBA/2 skin grafts against cotransferred conventional CD8(+) T cells. Functionally active immunoregulatory CD8(+) T cells also resided in donor skin allografts. Eighteen percent of CD8(+) suppressor T cells expressed @entity10867 as measured by flow cytometry, and produced reduced levels of IFN-y, @entity2047 , and @entity1618 in comparison to CD8(+) effector T cells as measured by ELISA. It is unlikely that CD8(+) suppressor T cells mediated graft protection via @entity1618 , as @entity1618 /Fc fusion protein impaired RPM-induced LTA in @entity1961 KO @entity19 . Our data supported the notion that RPM-induced suppressor CD8(+) T cells home to the allograft and exert donor-specific graft protection.
