T-cell-mediated Rejection of Vascularized Xenografts in the Absence of Induced Anti-donor Antibody Response

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Abstract
T cells are considered to play a major indirect role in the pathogenesis of xenograft vascular rejection, by promoting the induction of anti‐donor antibodies that trigger complement‐ and antibody‐dependent cell cytotoxicity. However, how vigorous the T cell xenoresponse is in vivo, and whether, besides their helper function, T cells are capable of directly affecting the graft is still unclear. We have previously shown that cyclosporine A (CsA) withdrawal in accommodated cardiac xenograft recipient allows for a rapid and dense T‐cell infiltration, concomitant to an acute graft rejection. In this paper we further characterize the role of T cells in this rejection process and we demonstrate that adoptive transfer of CD4+ T cells in irradiated recipients of long‐term cardiac xenografts is sufficient to trigger acute rejection, in the absence of any detectable induced anti‐hamster antibody response. Therefore, our data suggest that unusually strong T‐cell response will be another major barrier to xenotransplantation, even if antibody‐mediated vascular rejection is controlled.