Donor-specific immune regulation by CD8 lymphocytes expanded from rejecting human cardiac allografts.
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.
Dijke
I E
IE
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands. i.dijke@erasmusmc.nl
Caliskan
K
K
Klepper
M
M
de Kuiper
R
R
Balk
A H M M
AH
Maat
A P W M
AP
Weimar
W
W
Baan
C C
CC
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
D007166:Immunosuppressive Agents