title: Indirect presentation of donor histocompatibility antigens contributes to the allogeneic response against human cardiac myocytes.
abstract: Normal human cardiac myocytes failed to induce proliferative responses of peripheral blood mononuclear cells from major histocompatibility complex (MHC)-disparate individuals. Induction of cell-surface MHC antigens on such myocytes before culture still failed to induce alloproliferative responses. Similar data were obtained with cocultures of a human cardiac myocyte (W1) cell line and allogeneic lymphocytes. Addition of interleukin (IL)-1, IL-2, or IL-1 plus IL-2 failed to reconstitute the alloproliferative response. Of interest was the observation that preincubation of primary cultures of myocytes or the W1 cell line (especially after pretreatment with interferon-gamma) with an autologous enriched population of adherent cells, containing monocytes/macrophages/B cells, markedly augmented the ability of these cells to induce alloproliferative responses. In addition, the specificity of the secondary response of T cells primed against myocytes or the W1 cell line (especially after pretreatment of the myocytes or the W1 cell line with interferon-gamma) appeared to reside at the MHC type of the adherent cells used in the primary phase. These data suggest that adherent cells most likely present donor myocyte-specific MHC or other proteins to allogeneic T cells in the context of the MHC molecules of the adherent cells. Such a finding provides evidence that the indirect pathway of host cellular sensitization may occur in vivo and play a role in chronic graft rejection.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Ga.
authors.forename: A A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Kanter
authors.forename: N
authors.initials: N
authors.lastname: Naucke
authors.forename: K W
authors.initials: KW
authors.lastname: Sell
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology; D009206:Myocardium / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II