Different Effects of Interleukin 21 and Interleukin 15 on In Vitro Expanded CD8+T Cells Stimulated by Alloantigen

Objective. To investigate the effects of IL (interleukin) 21 on CD8(+) T cells stimulated by alloantigen in the presence of IL-15 in vitro. Methods. CD8(+) T cells sorted with MicroBeads from fresh human peripheral blood mononuclear cells were cocultured with antigen-presenting cells derived from HLA-A, -B, and -DR full-mismatched individuals for 9 days without any cytokines, in the presence of IL-15, IL-21, and IL-15 combined with IL-21, respectively. The proliferation and phenotypic characteristics of CD28(+) and CD28(-) subsets were measured after 9 days of culture. Results. The proliferation of CD8(+) T cells can be promoted either by IL-15 alone or in combination with IL-21 compared with IL-21. Cells expanded in the presence of IL-15 are mainly CD8(+)CD28(-) T cells, while those expanded in the presence of IL-15 combined with IL-21 are mostly CD8(+)CD28(+) T cells. In the presence of IL-15, most CD8(+)CD28(+) T cells shifted to CD8(+)CD28(-) T cells during the process of proliferation, but In the presence of IL-15 combined with IL-21, CD8(+)CD28(+) T cells didn't shift to CD8(+)CD28(-) T cells during proliferation, moreover, CD8(+)CD28(-) T cells cannot transform in reverse to CD8+CD28(+) T cells. IL-21 combined with IL-15 can promote the expression of granzyme B and perforin in CD8(+)CD28(+) and/or CD8(+)CD28(-) T cells compared with IL-15 alone. Conclusion. IL-21 cannot promote the proliferation of CD8(+) T cells under allogeneic stimulation unless combined with IL-15. IL-21 prevents the loss of CD28 molecules caused by IL-15 but cannot promote its re-expression in CD28(-) T cells. CD8(+) T cells expanded by IL-21 combined with IL-15 is characterized by cytotoxic phenotype.