The influence of HLA-mismatches on phenotypic and functional characteristics of graft infiltrating lymphocytes after heart transplantation.
We studied the influence of HLA mismatches on T lymphocyte cultures that were derived from endomyocardial biopsies (EMB) from 118 heart transplant recipients. From patients with DR mismatches, the majority of the EMB-derived cultures were dominated by CD4, while in patients without DR mismatches, CD8 was the predominant T cell subset. The majority (75%) of the cultures were cytotoxic against donor antigens. A significantly (P < 0.005) lower proportion of the cultures showed cytotoxicity (36%) against HLA-A antigens when compared to HLA-B (53%) or HLA-DR (49%). A dose effect phenomenon was detected for all HLA antigens, including HLA-A: a higher number of A, B or DR mismatches resulted in a higher number of cytotoxic cultures directed against these antigens. B and DR matching had the greatest influence on 6 month freedom from rejection. Both our experimental and clinical data indicated that HLA matching played a role in the immune response against a transplanted heart.
Ouwehand
A J
AJ
Department of Thoracic Surgery, Erasmus University Rotterdam, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
Baan
C C
CC
Vaessen
L M
LM
Jutte
N H
NH
Balk
A H
AH
Bos
E
E
Claas
F H
FH
Weimar
W
W
D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006680:HLA Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors
D006680:HLA Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2