Cell interactions and cytokines in transplantation immunity.
Peripheral T cells usually harbor clones that can directly recognize allogeneic HLA molecules in association with hitherto undefined allogeneic peptides. However, recognition does not lead to activation of allograft immunity, unless the allogeneic cells are professional ISCs. In the absence of such cells in the graft, activation of specific alloimmunity might occur indirectly by host ISCs presenting graft-derived allogeneic peptides. Such peptides are thought to often be derived from allogeneic HLA molecules themselves. A local inflammation followed by activation of endothelial cells could facilitate the migration of immunocompetent cells into the graft parenchyma and stimulation by dendritic cells in the graft. A local inflammation is believed to be induced by ischemic damage to cells in the graft, to postoperative aseptic inflammation associated with wound healing and repair, or by ongoing local infection. Naive or virgin T cells primarily migrate to secondary lymphoid organs and specific subsets of T cells traffic selective organs such as the gut or lymph nodes. However, memory T cells extravasate to sites of local inflammation. Therefore, prior T-cell alloimmunity, which might be the result of immunity against cross-reactive self-HLA restricted foreign peptides, as well as a local inflammatory reaction in the graft, caused by tissue damage or mediated by preexisting low levels of noncytotoxic antibodies, might facilitate graft rejection.
Möller
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Division of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement; D016207:Cytokines / Q000502:physiology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007249:Inflammation; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology
D016207:Cytokines; D006680:HLA Antigens