title: The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8+ T lymphocytes in endomyocardial biopsy derived T cell cultures.
abstract: 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+ patients (58%) and 27/46 TCAD- patients (57%) were analysed. The TCAD+ patients had, compared with the TCAD- patients, a higher median percentage of CD8+ T cells (71% versus 25%, P = 0.06) and a lower median percentage of CD4+ 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+ and TCAD- 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+ cells in cultures from TCAD- and TCAD+ patients shows that other factors besides CD8+ T cells also play a role.
authors.affiliation: Department of Internal Medicine I, Erasmus University/University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: N H
authors.initials: NH
authors.lastname: Jutte
authors.forename: K
authors.initials: K
authors.lastname: Groeneveld
authors.forename: A H
authors.initials: AH
authors.lastname: Balk
authors.forename: A J
authors.initials: AJ
authors.lastname: Ouwehand
authors.forename: E H
authors.initials: EH
authors.lastname: Loonen
authors.forename: M
authors.initials: M
authors.lastname: Van der Linden
authors.forename: S
authors.initials: S
authors.lastname: Strikwerda
authors.forename: B
authors.initials: B
authors.lastname: Mochtar
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003327:Coronary Disease / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology
chemical_list: D006680:HLA Antigens