AUTHOR=Hu Min , Hawthorne Wayne J. , Yi Shounan , O’Connell Philip J. TITLE=Cellular Immune Responses in Islet Xenograft Rejection JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.893985 DOI=10.3389/fimmu.2022.893985 ISSN=1664-3224 ABSTRACT=

Porcine islets surviving the acute injury caused by humoral rejection and IBMIR will be subjected to cellular xenograft rejection, which is predominately mediated by CD4+ T cells and is characterised by significant infiltration of macrophages, B cells and T cells (CD4+ and CD8+). Overall, the response is different compared to the alloimmune response and more difficult to suppress. Activation of CD4+ T cells is both by direct and indirect antigen presentation. After activation they recruit macrophages and direct B cell responses. Although they are less important than CD4+ T cells in islet xenograft rejection, macrophages are believed to be a major effector cell in this response. Rodent studies have shown that xenoantigen-primed and CD4+ T cell-activated macrophages were capable of recognition and rejection of pancreatic islet xenografts, and they destroyed a graft via the secretion of various proinflammatory mediators, including TNF-α, reactive oxygen and nitrogen species, and complement factors. B cells are an important mediator of islet xenograft rejection via xenoantigen presentation, priming effector T cells and producing xenospecific antibodies. Depletion and/or inhibition of B cells combined with suppressing T cells has been suggested as a promising strategy for induction of xeno-donor-specific T- and B-cell tolerance in islet xenotransplantation. Thus, strategies that expand the influence of regulatory T cells and inhibit and/or reduce macrophage and B cell responses are required for use in combination with clinical applicable immunosuppressive agents to achieve effective suppression of the T cell-initiated xenograft response.