The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8 super(+) T lymphocytes in endomyocardial biopsy derived T cell cultures

Long-term survival of heart transplant recipients is limited by the development of transplant coronary artery disease (TCAD). We analysed whether the development of TCAD is correlated with the incidence of acute rejection episodes, with the formation of anti-HLA antibodies or with the composition and function of T lymphocyte cultures derived from endomyocardial biopsies. TCAD was assessed by visual analysis of annually performed coronary angiograms and defined as the presence of all vascular changes, including minor wall irregularities. One year after transplantation, 31 of the 77 patients studied had TCAD (40%). The median age and mean number of HLA mismatches in patients with or without TCAD were highly comparable. The patient groups did not differ in incidence of acute rejection episodes, nor in percentage of endomyocardial biopsies yielding T cell cultures. At 1 year after transplantation, lymphocyte cultures from 18/31 TCAD super(+) patients (58%) and 27/46 TCAD super(-) patients (57%) were analysed. The TCAD super(+) patients had, compared with the TCAD super(-) patients, a higher median percentage of CD8 super(+) T cells (71% versus 25%, P = 0 times 06) and a lower median percentage of CD4 super(+) T cells (4% versus 40%, P = 0.04). Similar differences were found in a longitudinal analysis of the culture results of endomyocardial biopsies (EMBs) obtained during the first year. The cytotoxic reactivity of the cultures against donor HLA class I or class II antigens was comparable in the two groups, although a difference in recognition of heart specific antigens remains possible. The fact that EMB-derived cultures from TCAD super(+) and TCAD super(-) patients differed in T cell phenotype populations gives some support to the hypothesis that cellular immunological processes are involved in the development of TCAD. However, while the median values differed, the overlap of the percentages of CD8 super(+) cells in cultures from TCAD super(-) and TCAD super(+) patients shows that other factors besides CD8 super(+) T cells also play a role.