CHARACTERIZATION OF THE CYTOTOXIC ALLORESPONSE OF CORD-BLOOD

As compared to hone marrow, transplantation with cord blood (CB) is as sociated with a lower risk of GVHD, Although some cases of GVHD III ha ve been reported, usually the grade of GVHD remains low, even when don or and recipient are not fully HLA matched. To investigate whether thi s is due to an intrinsic property of CB T cells, we studied the condit ions under which CB CD8(+) cells would be able to generate an alloresp onse. In addition, we measured the cytokines secreted by the alloreact ive cytotoxic T lymphocyte (CTL) clones generated, We show that: (1) t he capacity of CB cells to generate alloreactive CTLs in vitro is dimi nished as compared to adult cells (AB); (2) in the presence of exogeno us IL-2, CB cells do generate a normal alloreactive response; (3) alth ough CB-derived CD8(+) allospecific clones showed the same T1/T0 cytok ine profile as the clones from AB, they secreted a lower amount of IFN -gamma; and (4) in addition, cloned CD4(+) CB cells are mainly T2/T0 t ype, whereas AB CD4(+) T cells were mainly of T1/T0 type. These data s uggest that the reduced GVHD observed after transplantation with CB mi ght be the result of the naiveness of CD T cells, After allostimulatio n, CB cytotoxic T cells differ from AB T cells by a higher activation threshold, a lower secretion of IFN-gamma by both CD4(+) and CD8(+) CB cells and their bias towards a T2 type CD4 response.