PROLIFERATIVE AND CYTOTOXIC RESPONSES OF HUMAN CORD-BLOOD T-LYMPHOCYTES FOLLOWING ALLOGENEIC STIMULATION

On the basis of the success of recent cord blood transplants, we undertook a comparison of the proliferative and cytotoxic potential, following allogeneic stimulation, of E-rosetted T cells from cord blood or adult peripheral blood (PB3) or bone marrow (BM). The magnitude of the proliferative response of cord blood (CB) T cells to alloantigen was greater than or equal to that of adult PB or BM T cells. Proliferation following culture with IL-2, IL-4, or IL-7 produced a similar result. In contrast, the cytotoxic activity in 1 degrees, 2 degrees, or 3 degrees mixed leukocyte culture of CB T cells was minimal, typically less than 20% at an effector:target ratio of 100:1. Cytometric analysis of CB T cell populations before and after culture with allostimulation demonstrated similar ratios of CD4(+) and CD8(+) cells in cultures of CB and adult T cells. Down-regulation of CD45RA antigen expression, a measure of CD4(+) cell activation, was comparable in adult and CB cultures. Activation of CD8(+) CTL effecters was assessed by the acquisition of CD28 antigen expression. After culture, a smaller proportion of CD8(+)CD28(+) effector cells was present in CB cultures as compared to adult T cell cultures. Thus, following in vitro priming with alloantigen CB T cells generate a vigorous proliferative response yet produce little antigen-specific cytotoxicity. This diminished cytotoxicity may, in part, be related to the low incidence of graft vs host disease thus far noted in human CB transplants. (C) 1994 Academic Press, Inc.