DIFFERENTIAL EXPRESSION OF CD40L ON CORD BLOOD CD4/CD8 AND CD45RA/CD45RO ACTIVATED MONONUCLEAR CELLS.
          I Chalmers, M Contreras and CV Navarrete, Department of Histocompatibility and Immunogenetics, NBS, London and the South East Zone, UK.
          CD40L is expressed predominantly on activated T cells and plays an important role in humoral and cell mediated responses. Both these responses are involved in the pathogenesis of GVHD and it is therefore likely that CD40-CD40L interactions may play a role in the reduced incidence and severity of GVHD observed following cord blood transplantation. In this study, PMA and Ionomycin activated cord blood (CB) and adult blood (AB) CD4/CD8 and CD45RA/CD45RO cells were studied for the expression CD40L using three colour flow cytometry. The results showed that although the kinetics of CD40L expression was similar in both CB and AB cells (peak between 8 and 10 hours), CB showed a reduced level of CD40L expression compared with AB (13% vs 25%). In contrast, the expression on an early activation marker, CD69, was similar in CB and AB ( 69% vs 65%). Further subset analysis showed that expression of CD40L on CB cells was similar in CD4+ and CD8+ cells (5% vs 7%) whereas in AB there was a higher ( but not significant) level of CD40L expression on CD4+ than on CD8+ cells (21% vs 15%) . Furthermore in CB, the majority of CD40L expression was found on the CD45RA subset whereas in AB it was on the CD45RO subset. There are several reasons that may explain the reduced CD40L expression on CB cells including the already described reduced secretion of cytokines such as IL-2 and gamma INF, since previous studies have shown the importance of these cytokines in the regulation of CD40L expression. Whatever the mechanism involved, the reduced expression of CD40L on CB cells may affect the lower incidence of GVHD observed in patients after cord blood transplantation.