TRANSFORMING GROWTH FACTOR-β AND INTERLEUKIN-10 SUBVERT ALLOREACTIVE DELAYED TYPE HYPERSENSITIVITY IN CARDIAC ALLOGRAFT ACCEPTOR MICE1


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Abstract

We have previously reported that temporary treatment of cardiac allograft recipients with gallium nitrate (GN) results in indefinite graft survival, and the inability to mount donor-reactive delayed type hypersensitivity (DTH) responses.We report that antibodies to either transforming growth factor-β (TGFβ) or interleukin-10 (IL10) can uncover DTH responses to donor alloantigens in cardiac allograft acceptor mice. The DTH responses uncovered with TGFβ-reactive antibodies can be blocked by exogenous IL10, and those uncovered with IL10-reactive antibodies can be blocked by exogenous TGFβ. These data demonstrate that allograft acceptor mice are fully allosensitized, and poised to make donor-reactive cell-mediated immune responses. However, such responses are subverted by a donor alloantigen-dependent mechanism that involves TGFβ and IL10, which in turn interfere with local cell-mediated immune responses.

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