Indirect presentation of donor histocompatibility antigens contributes to the allogeneic response against human cardiac myocytes.
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.
Ansari
A A
AA
Department of Pathology, Emory University School of Medicine, Atlanta, Ga.
Wang
Y C
YC
Kanter
K
K
Naucke
N
N
Sell
K W
KW
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
D000949:Histocompatibility Antigens Class II