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

Abstract 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.