An in vitro model of allogeneic stimulation of cord blood - Induction of Fas independent apoptosis

Cord blood is increasingly used in transplantation as it is a readily avail able source of progenitor cells and is reputed to generate less severe graf t-versus-host disease (GVHD) than adult bone marrow. We have compared apopt osis of cord blood lymphocytes (CB) and adult lymphocytes (PBMC) after stim ulation via HLA class I, HLA class II or CD3 in order to reproduce in vitro some of the stimuli ocurring after allotransplantation. CB spontaneously apoptose more than PBMC ex vivo, stimulation via HLA class I dramatically increased CB apoptosis without altering viability of PBMC. Expression of Fas was markedly lower on CB than on PBMC and this difference was maintained even after activation. Fas ligand Tvas expressed in CB and in PBMC. CB were activated via either HLA class I or class II molecules although pro liferation mas not observed. Only phorbol ester pre-activation allowed Fas to subsequently induce a death signal. Proliferation of PBMC via CD3 led to enhanced Fas signals. CB therefore differ from PBMC with regard to both sp ontaneous and activation induced apoptosis and either allo- or CD3 mediated stimulation, Finally, the apoptosis of CB via HLA-class I could have an im portant role in the moderation of graft-versus-hose disease. Human Immunolo gy 60, 598-607 (1999). (C) American Society for Histocompatibility and Immu nogenetics, 1999. Published by Elsevier Science Inc.