IL-30 is required for regulatory T cells to mediate tolerance to alloantigens in vivo

We present evidence that donor-reactive CD4+ T cells present in mice tolera nt to donor alloantigens are phenotypically and functionally heterogeneous. CD4+ T cells contained within the CD45RB(high) fraction remained capable o f mediating graft rejection when transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD54RB(low) CD4(+) and CD25(+)CD4(+) populations failed to induce rejection, but rather, were able to inhibit re jection initiated by naive CD45RB(high) CD4(+) T cells, Analysis of the mec hanism of immunoregulation transferred by CD45RB(low) CD4(+) T cells in viv o revealed that it was donor Ag specific and could be inhibited by neutrali zing Abs reactive with IL-10, but not IL-4, CD45RB(low) CD4(+) T cells from tolerant mice were also immune suppressive in vitro, as coculture of these cells with naive CD45RB(high) CD4(+) T cells inhibited proliferation and T h1 cytokine production in response to donor alloantigens presented via the indirect pathway. These results demonstrate that alloantigen-specific regul atory T cells contained within the CD45RB(low) CD4(+) T cell population are responsible for the maintenance of tolerance to donor alloantigens in vivo and require IL-10 for functional activity.