title: Persistence of donor-specific IL-2-secreting cells and cytotoxic T lymphocyte precursors in human kidney transplant recipients evidenced by limiting dilution analysis.
abstract: The low reactivity to donor alloantigens reported in PBL from kidney transplant recipients might be related to clonal deletion and/or suppression of donor-specific alloreactive cells. To discriminate between these two hypotheses, we quantified the number of IL-2 secreting cells (IL-2-SC) and of cytotoxic precursors (CTLp) in the T cells from tolerant recipients when stimulated with either donor specific or nonrelated third-party LCL. To eliminate the irrelevant reactivity, we used as responding cells high-density T cells that had been depleted of such reactivity by 4 days preculture with autologous lymphoblastoid cell line in the presence of bromodeoxyuridine. Thus, frequencies of IL-2-SC and CTLp specifically directed at alloantigens could be measured. In 11 recipients, there was no strong decrease in the frequency of donor-reactive T cells when compared to the frequency of those directed at a third-party lymphoblastoid cell line, either for IL-2-SC (tested in 11 patients) or for CTLp (tested in 6 patients). In three cases of seven, a suppression was observed only when T cells were stimulated by donor cells. These data suggest that donor-reactive cells are still present in PBL of kidney-transplant recipients tested from 6 mo to 4 y posttransplantation. Moreover, suppression of donor-specific cells can be demonstrated in peripheral T cells of some recipients, which may account in part for the absence of rejection.
authors.affiliation: Laboratoire d'Immunologie Cellulaire et de Transplantation, ER 277 CNRS, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
authors.forename: O
authors.initials: O
authors.lastname: Lantz
authors.forename: P
authors.initials: P
authors.lastname: Alard
authors.forename: M H
authors.initials: MH
authors.lastname: Ben Aribia
authors.forename: G
authors.initials: G
authors.lastname: Chavanel
authors.forename: D
authors.initials: D
authors.lastname: Fries
authors.forename: A
authors.initials: A
authors.lastname: Senik
authors.forename: B
authors.initials: B
authors.lastname: Charpentier
mesh_terms: D006648:Histocompatibility; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000378:metabolism*; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D007376:Interleukin-2; D007519:Isoantigens