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 current investigation, we determined the capacity of tumour necrosis factor-alpha (TNF-alpha) to induce apoptosis in human naïve T cells in cord blood, and assessed the roles of two distinct TNF receptors (TNFRs) in mediating death signals. After activation, cord blood T cells were sensitive to TNF-alpha-induced apoptosis, and interleukin 2 (IL-2) could prevent this apoptotic response. Both TNFR1 (p55) and TNFR2 (p75) expressed on activated cord blood T cells were able to transmit apoptotic signals. Moreover, a synergistic effect was observed by a combination of TNFR1- and TNFR2-signals. Additionally, CD4(+) T cells showed higher sensitivity to TNFR-mediated apoptosis than CD8(+) T cells. These data suggest that TNF-alpha probably is a mediator 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.