Susceptibility to Fas and tumor necrosis factor-α receptor mediated apoptosis of anti-CD3/anti-CD28-activated umbilical cord blood T cells

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Abstract

Decreased severity of graft-versus-host disease after mismatched umbilical cord blood (UCB) transplantation may be attributed in part to the increased propensity to apoptosis of UCB T cells following activation. Interleukin (IL)-15, a pleiotropic cytokine that is essential for T-cell proliferation and survival, may serve as promising immunomodulative therapy post-CB transplantation for its anti-apoptotic effect. This study aimed to determine the kinetics of Fas or tumor necrosis factor-α receptor (TNFR) mediated caspase-3 expression and apoptosis of anti-CD3/anti-CD28 activated UCB T cells in the influence of IL-15. Activated caspase-3 expression was analyzed by Western blotting and the percentage of apoptotic cells was determined by annexin-V/propidium iodide (PI) flow cytometric staining. Significant expression of Fas and TNFR2 was detected on anti-CD3/anti-CD28 pre-activated UCB T cells. These cells were susceptible to anti-Fas but not TNF-α-induced apoptosis. Kinetic study shows that caspase-3 expression became evident at 6th-8th h following anti-Fas stimulation, while early apoptotic cells with annexin-V+/PI− expression appeared at 12th-16th h. IL-15, though successful in decreasing apoptosis in pre-activated UCB T cells, failed to completely prevent Fas-mediated caspase-3 expression and apoptosis of CB T cells. The pre-activated UCB and adult peripheral blood T cells behaved similarly with regard to death receptor expression, caspase-3 expression and apoptosis upon Fas-engagement. Although IL-15 promotes overall activated UCB T-cell survival, it did not particularly prevent Fas-mediated activation-induced cell death.

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