Cord blood transplantation: implications for graft vs. host disease and graft vs. leukemia.

Cord blood (CB) was analyzed for its alloreactive immune potential to evaluate its capacity to mediate graft vs. host disease (GVHD) and graft vs. leukemia (GVL) effects. Cord blood was observed to display minimal innate cytotoxic capacity but was capable of rapidly developing significant nonspecific natural killer cell-like effector mechanisms. Cord blood was unable to generate effective alloantigen-specific cytotoxic T lymphocytes (CTL), which was at least partially due to an altered lymphokine profile. The frequency of alloreactive T cells present in CB (whether assessed as total responding T-cell or CTL precursors) was greatly reduced as compared to adult peripheral blood lymphocytes (PBLs). However, the frequency of nonspecific effector cells was equivalent to PBLs. Significantly, CB T cells seemed to have undergone some type of developmental tolerance to maternal HLA antigens in utero, which could greatly increase the utility of CB in familial transplants. That is, CB T cells were unresponsive to noninherited maternal HLA antigens. Finally, CB demonstrated significant GVL capacity whether measured in vitro or in an animal model in vivo. Thus, the use of CB in most transplant settings should be free of the immunological problems associated with GVHD yet still be an effective mediator of GVL.