Tumour necrosis factor-alpha-induced apoptosis in cord blood T lymphocytes: involvement of both tumour necrosis factor receptor types 1 and 2

Cord blood T cells are much more likely to be induced to apoptosis in vitro than adult T cells. Nevertheless, the expression of Fas is markedly lower on cord blood lymphocytes than on peripheral blood lymphocytes. In the curr ent investigation, we determined the capacity of tumour necrosis factor-alp ha (TNF-alpha) to induce apoptosis in human naive T cells in cord blood, an d assessed the roles of two distinct TNF receptors (TNFRs) in mediating dea th signals. After activation, cord blood T cells were sensitive to TNF-alph a -induced apoptosis, and interleukin 2 (IL-2) could prevent this apoptotic response. Both TNFR1 (p55) and TNFR2 (p75) expressed on activated cord blo od T cells were able to transmit apoptotic signals. Moreover, a synergistic effect was observed by a combination of TNFR1- and TNTFR2-signals. Additio nally, CD4(+) T cells showed higher sensitivity to TNTR-mediated apoptosis than CD8(+) T cells. These data suggest that TNF-alpha probably is a mediat or of apoptosis in cord blood T cells in vivo and may contribute to the low incidence of graft-versus-host disease in cord blood transplantation.