Susceptibility to Fas and tumor necrosis factor-alpha receptor mediated apoptosis of anti-CD3/anti-CD28-activated umbilical cord blood T cells.
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-alpha 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-alpha-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.
Lin
Syh-Jae
SJ
Division of Asthma, Allergy and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Lee
Chen-Cheng
CC
Cheng
Po-Jen
PJ
See
Lai-Chu
LC
Kuo
Ming-Ling
ML
D017304:Annexin A5 / Q000187:drug effects / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology*
D017304:Annexin A5; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D053148:Caspase 3