title: Donor-specific immune regulation by CD8 lymphocytes expanded from rejecting human cardiac allografts.
abstract: To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic-stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T-cell response of PBMC, but not the anti-third-party response. Interestingly, it was the CD8(+) GL subset of these cultures that inhibited the antidonor response (65-91% inhibition of the proportion of proliferating cells); the CD4(+) GLs of the expanded GL cultures were not suppressive. In conclusion, CD8(+) GLs expanded from rejecting human cardiac allografts can exhibit donor-specific immune regulatory activities in vitro. We suggest that during acute cellular rejection, GLs may not only consist of graft-destructing effector T cells, but also of cells of the CD8(+) type with the potential to specifically inhibit antidonor immune reactivity.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands. i.dijke@erasmusmc.nl
authors.forename: I E
authors.initials: IE
authors.lastname: Dijke
authors.forename: K
authors.initials: K
authors.lastname: Caliskan
authors.forename: M
authors.initials: M
authors.lastname: Klepper
authors.forename: R
authors.initials: R
authors.lastname: de Kuiper
authors.forename: A H M M
authors.initials: AH
authors.lastname: Balk
authors.forename: A P W M
authors.initials: AP
authors.lastname: Maat
authors.forename: W
authors.initials: W
authors.lastname: Weimar
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000208:Acute Disease; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents