Development of autoantibodies to T cell clonotypic structures in a liver-kidney allograft recipient.
To elucidate the mechanism of human liver allograft rejection and acceptance, T cell clones were established from liver biopsies of a liver-kidney transplant recipient during a rejection episode. Five of the clones were characterized and found to be CD4+, alpha/beta positive T cells that proliferated specifically to the mismatched donor HLAs. Using an immunofluorescence assay, it was observed that three of these clones were recognized by autologous antibodies developed during the post-transplant period between 18 months and the end of the testing period of 36 months. Furthermore, by capping experiments, it was determined that these antibodies were recognizing the CD3-TCR complex. This was confirmed by immunoprecipitation and sequential immunoprecipitation followed by SDS-PAGE and autoradiography of lysates of radiolabeled T cell clones. Thus, our data indicate that donor-reactive T cells infiltrate into the liver allograft during rejection episodes, and that autologous antibodies reactive to the CD3-TCR complex of these cells are developed in the post-transplant period. These results support the hypothesis that the development of auto-antibodies directed against or cross-reactive to the clonotypic structures of the donor-reactive lymphocytes may play an important role in the down-regulation of the immune response against the allograft.
Duffy
B F
BF
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Mathew
J M
JM
Flye
M W
MW
Mohanakumar
T
T
D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D017252:CD3 Complex / Q000032:analysis; D002478:Cells, Cultured; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D001323:Autoantibodies; D017252:CD3 Complex; D007074:Immunoglobulin G