Differential cyclosporin-A sensitivity on survival and activation of umbilical cord and adult peripheral blood CD4+ T cells.
Enhanced cyclosporine-A (CsA) sensitivity of umbilical cord blood (CB) CD4(+) T cells may contribute to the lower incidence of graft-versus-host disease (GVHD) after mismatched CB transplantation. Interleukin (IL)-15, an IL-2 like gamma-chain signaling cytokine, may bypass CsA inhibition and play an important role in GVHD pathogenesis. The present study examines CsA sensitivity of IL-15-driven CB CD4(+) T cell survival, activation and proliferation, comparing adult peripheral blood (APB) CD4(+) T cell responses. We establish that (1) resting CB CD4(+) T cells were more susceptible to CsA-induced cell death than their adult counterpart; (2) IL-15 help support the survival of resting CB CD4(+) T cell under the influence of CsA, though to a lesser degree that observed in adults; (3) higher CsA sensitivity of CD25 up-regulation following TCR activation was observed in CB but more readily counteracted by IL-15 compared to adults; (4) IL-15-driven proliferation of TCR-activated CD4(+) T cells was more susceptible to CsA inhibition than corresponding adults; and (5) TCR-activated CB CD4(+) T cells surviving high dose CsA (5 microg/ml) in IL-15-supplemented cultures expressed significantly lower percentages of CD45RO(-)/CD25(+) subsets compared to corresponding APB. Taken together, the differential CsA sensitivity and IL-15 response between CB and APB CD4(+) T cells may contribute to the lessened GVHD severity in the setting of CB transplantation.
Lin
Syh-Jae
SJ
Division of Allergy/Immunology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, College of Medicine, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan. sjlino@adm.cgmh.org.tw
Kuo
Ming-Ling
ML
Cheng
Po-Jen
PJ
Hsiao
Shiu-Shan
SS
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine