title: Characteristics of graft-infiltrating lymphocytes after human heart transplantation. HLA mismatches and the cellular immune response within the transplanted heart.
abstract: The influence of HLA mismatches between donor and recipient on the phenotypes, function, and specificity of T-lymphocyte cultures derived from endomyocardial biopsies was studied in 118 heart transplant recipients. In case of HLA-DR mismatches, the majority of the EMB-derived cultures were dominated by CD4+ T cells while, in patients with HLA-A and -B mismatches but without DR mismatches, CD8+ T cells comprised the predominant T-cell subset. Cytotoxicity against donor antigens was observed in 75% of the cultures. A significantly (p < 0.005) lower proportion of the cultures showed cytotoxicity against HLA-A antigens (36%) when compared with HLA-B (53%) or HLA-DR (49%). An HLA-A2 mismatch elicited a cytotoxic response that was comparable to that found against HLA-B and -DR antigens: 62% of the cultures from HLA-A2 mismatched donor-recipient combinations was reactive against A2. A higher number of A, B, or DR mismatches resulted in a higher number of cytotoxic cultures directed against these antigens. A higher number of HLA-B and -DR mismatches was associated with a lower freedom from rejection. Our data indicate that, despite the use of adequate immunosuppressive therapy, the degree of HLA matching plays a crucial role in the immune response against a transplanted heart, resulting in a significant effect on freedom from rejection.
authors.affiliation: Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ouwehand
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.forename: L M
authors.initials: LM
authors.lastname: Vaessen
authors.forename: N H
authors.initials: NH
authors.lastname: Jutte
authors.forename: A H
authors.initials: AH
authors.lastname: Balk
authors.forename: E
authors.initials: E
authors.lastname: Bos
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000208:Acute Disease; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009206:Myocardium / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents