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.