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Susceptibility to Fas and tumor necrosis factor‐α receptor mediated apoptosis of anti‐CD3/anti‐CD28‐activated umbilical cord blood T cells
Author(s) -
Lin SyhJae,
Lee ChenCheng,
Cheng PoJen,
See LaiChu,
Kuo MingLing
Publication year - 2009
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/j.1399-3038.2008.00790.x
Subject(s) - apoptosis , annexin , propidium iodide , cd28 , medicine , tumor necrosis factor alpha , fas ligand , cd3 , fas receptor , cancer research , il 2 receptor , immunology , t cell , microbiology and biotechnology , flow cytometry , programmed cell death , biology , immune system , cd8 , biochemistry
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.