Cellular Immune Responses in Islet Xenograft Rejection

• Published in: Frontiers in immunology Vol. 13; p. 893985
• Main Authors: Hu, Min, Hawthorne, Wayne J., Yi, Shounan, O’Connell, Philip J.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 07-07-2022
• Subjects: IBMIR; Immunology; islet (cell) transplantation; macrophage cell; T cell; transgenic pig; xenograft
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.893985

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.