Abstract

Organ shortage continues to be the forefront of problems facing clinical transplantation. Although xenografts serve as a promising alternative, its success is contingent upon further investigation into the mechanisms of cell-mediated xenograft rejection. Here, we explored the direct and indirect contribution of human immune cells in xenorecognition using human and murine in vitro coculture systems. Our data shows that human T cells directly recognized the xenogeneic MHC molecules since blocking of MHCs suppressed their proliferative response and cytokines production of IL-2 and IFN-γ. While B and NK cells alone did not generate a significant response, the combination of B and T cells promoted indirect xenorecognition by T cells as evidenced by an increase in B cell proliferative response. Overall, our data suggests that human T cells have the plasticity to recognize xenogeneic MHCs and contribute to xenograft rejection.

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