Altered specificity of alloreactive cardiac graft-infiltrating cells by prophylactic treatment with OKT3 or horse antilymphocyte globulin.
Graft-infiltrating lymphocytes from patients who were prophylactically treated with OKT3 or horse antilymphocyte globulin (H-ALG) were found to have different specificity patterns from those in the control group that received cyclosporine from the day of transplantation. This prophylactic treatment led to a significant decrease of the HLA-DR-directed cytotoxicity, while the cytolytic response against HLA-class I mismatches was hardly affected. In H-ALG patients without rejection, the percentages of class I-reactive cultures were found to be lower than in the other treatment groups, which was mainly due to a lower percentage of HLA-B--reactive cultures. In CsA and OKT3 patients, cytotoxic T cells were rather directed to HLA-B mismatches than to HLA-A antigens, while in H-ALG patients no difference in HLA-A and B-directed cytotoxicity was found. Our data suggest that OKT3 and H-ALG influence the specificity of the T cell allorepertoire, resulting in a decreased frequency of class II-specific cytotoxic T cells after transplantation. H-ALG also has a downregulating influence on the CTL response against HLA class I (HLA-B) antigens. In some patients a fast regeneration of these cells occurs, which results in a higher rejection incidence during the first posttransplant year.
Ouwehand
A J
AJ
Department of Thoracic Surgery, Erasmus University, Rotterdam, The Netherlands.
Baan
C C
CC
Groeneveld
K
K
Balk
A H
AH
Jutte
N H
NH
Bos
E
E
Claas
F H
FH
Weimar
W
W
D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use*; D004699:Endocardium / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000961:Antilymphocyte Serum; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D016853:Muromonab-CD3; D016572:Cyclosporine