THE FREQUENCY AND AVIDITY OF COMMITTED CYTOTOXIC T-LYMPHOCYTES (CCTL)FOR DONOR HLA CLASS-I AND CLASS-II ANTIGENS AND THEIR RELATION WITH GRAFT VASCULAR-DISEASE

Cellular immune processes may trigger the development of graft vascula r disease (GVD). CD4 and CD8 cytotoxic T lymphocytes that infiltrate t he allograft could play a role in the development of GVD. We studied t he presence of in vivo primed or committed CTL (cCTL) and their avidit y for donor HLA class I and class II antigens in graft-infiltrating ly mphocyte cultures propagated from endomyocardial biopsies derived from patients with and without signs of GVD. The fraction of cCTL with hig h avidity for HLA class I or class II antigens was estimated by the ad dition of anti-CD8 or anti-CD4 MoAbs to the cytotoxic phase of the lim iting dilution analysis. In the first year after transplantation no di fference in the frequency of donor-specific class I cCTL between patie nts with and without GVD was found. Addition of anti-CD8 MoAb revealed that most cultures predominantly consisted of cCTL with low avidity f or donor HLA class I antigens, irrespective of the development of GVD at 1 year after transplantation. However, in patients who did not deve lop GVD, the frequency of cCTL with donor HLA class II specificity was significantly higher than in patients who did develop GVD. The avidit y for donor HLA class II antigens was comparable in both groups. A hig h frequency of donor-specific cCTL for HLA class II antigens seems to be a protective factor against the development of GVD. These cCTL migh t be cytotoxic for cells involved in GVD development, e.g. activated e ndothelium and smooth muscle cells of donor origin.