title: Kinetics of circulating cytotoxic T lymphocyte precursors that have a high avidity for donor antigens: correlation with the rejection status of the human cardiac allograft.
abstract: Studies on graft infiltrating cells demonstrated that accumulation of cytotoxic T lymphocytes (CTL) with high avidity for donor antigens (Ag) coincided with acute cardiac rejection. In the present study, we analyse whether such high-avidity CTL are present within the peripheral blood of cardiac transplant recipients and whether their kinetics correspond with the rejection status of the allograft. Using limiting dilution analysis (LDA), donor-specific CTL were enumerated in serial blood samples of seven patients. From each patient, 7-11 samples were obtained during the first year after transplantation and up to three samples were obtained at a later date. Enumerated donor-specific CTL were divided into CTL with high or low avidity for donor Ag, depending on their sensitivity to CD8-blocking. In contrast to the situation in the graft, the donor-specific CTL present within the peripheral blood were CTL precursors (pCTL) and not fully mature CTL (cCTL). The number of donor-specific pCTL among peripheral blood cells fluctuated irrespective of the rejection grade of the allograft, indicating that the frequency of circulating donor-specific CTL does not reflect the immunological status of the allograft. During acute cardiac rejection, 66% (median) of the circulating donor-specific pCTL had a high avidity for donor Ag. This percentage significantly exceeded pre- and postrejection values obtained during the first year post-transplantation (median, 39% and 37%, respectively). The disparity in avidity increased even further more than 1 year after transplantation, when stable engraftment was achieved. Among donor-specific pCTL in peripheral blood, those with a high avidity were absent (median, 0%). Hence the avidity of circulating donor-specific CTL might inform us about the immune status of the cardiac allograft.
authors.affiliation: Department of Internal Medicine I, University Hospital-Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
authors.forename: N E
authors.initials: NE
authors.lastname: van Emmerik
authors.forename: L M
authors.initials: LM
authors.lastname: Vaessen
authors.forename: C J
authors.initials: CJ
authors.lastname: Knoop
authors.forename: C R
authors.initials: CR
authors.lastname: Daane
authors.forename: A H
authors.initials: AH
authors.lastname: Balk
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: D000941:Antigens / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000941:Antigens