title: Regulation of CD28 expression on umbilical cord blood and adult peripheral blood CD8+ T cells by interleukin(IL)-15/IL-21.
abstract: Interleukin (IL)-15 and IL-21, both belonging to common γ-chain-signaling cytokine family, have an important role to maintain homeostatic proliferation of CD8(+) T cells. CD28, an essential co-stimulatory molecule on T cells, may be a marker of replicative senescence. We investigated the effect of IL-15 and IL-21, alone or in combination, on activation, apoptosis, cytokine production and cytotoxic function of magnetic bead purified umbilical cord blood (UCB) and adult peripheral blood (APB) CD8(+) T cells with regards to their CD28 expression. We established that (1) IL-15-induced CD8(+) T cell proliferation was associated with a preferential expansion of CD28(-) population in UCB, which could be partially counteracted by IL-21; (2) UCB CD8(+) T cells were more readily responsive to IL-15 compared to their adult counterparts in terms of CD69 expression, with the majority of CD69-bearing CD8(+) T cells were CD28(-); (3) IL-21 further promoted interferon-gamma, but not tumor necrosis factor-alpha production from IL-15 treated CD8(+) T cells; (4) IL-21 also synergized with IL-15 to enhance perforin and granzyme B expression of CD8(+) T cells, especially in APB CD8(+)CD28(-) subsets; (5) IL-21 resulted in CD8(+) T cells apoptosis both in APB and UCB cells, mainly in CD8(+)CD28(-) subsets. Taken together, we demonstrate differential IL-15/IL-21 response in UCB CD8(+) T cells with regards to CD28 expression. Our results suggest that combining IL-21 and IL-15 immunotherapy may be better than IL-15 alone to ameliorate graft-versus-host disease while preserving antitumor effect in the post-UCB transplantation period.
authors.affiliation: Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chen
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Cheng
authors.forename: Hsiu-Shan
authors.initials: HS
authors.lastname: Hsaio
authors.forename: Pei-Tzu
authors.initials: PT
authors.lastname: Lee
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects; D006086:Graft vs Host Disease; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D054353:Perforin / Q000096:biosynthesis; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D000098546:Interleukin-21
chemical_list: D018106:CD28 Antigens; D019409:Interleukin-15; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; D000098546:Interleukin-21