Transforming growth factor-beta and interleukin-10 subvert alloreactive delayed type hypersensitivity in cardiac allograft acceptor mice

We have previously reported that temporary treat ment of cardiac allograft recipients with gallium nitrate (GN) results in indefinite graft survival, and the inability to mount donor-reactive delayed type hypersensitivity (DT H) responses. We report that antibodies to either transforming growth facto r-beta (TGF beta) or interleukin-10 (IL10) can uncover DTH responses to don or alloantigens in cardiac allograft acceptor mice. The DTH responses uncov ered with TGF beta-reactive antibodies can be blocked by exogenous IL10, an d those uncovered with IL10-reactive antibodies can be blocked by exogenous TGF beta. These data demonstrate that allograft acceptor mice are fully al losensitized, and poised to make donor-reactive cell-mediated immune respon ses. However, such responses are subverted by a donor alloantigen-dependent mechanism that involves TGF beta and IL10, which in turn interfere with lo cal cell-mediated immune responses.