IL-21 Prevents Expansion of CD8+CD28- T Cells Stimulated by IL-15 and Changes Their Subset Distribution

作者：Xie, Lu; Zhang, Zedan; Zhu, Ping; Tian, Kaiwen; Liu, Yanjun^*; Yu, Yuming^*

来源：Transplantation Proceedings, 2021, 53(7): 2407-2414.

DOI：10.1016/j.transproceed.2021.07.039

• DIFFERENTIATION

Background. To examine the effect of interleukin (IL)-21 on the proliferation, subsets, and immunological characteristics of CD8(+)CD28(-) T cells stimulated by IL-15 in vitro. @@@ Methods. Purified CD8(+) T cells stimulated with allogeneic CD2(-) cells obtained from the peripheral blood mononuclear cells of healthy volunteers were cocultured in the presence of IL-15 alone or IL-21 and IL-15 combined. The dynamic changes in the proliferation, subsets, and phenotypic characteristics of CD8(+)CD28(-) T cells were detected. Our work, involving human participants, complied with the Declaration of Helsinki and the Declaration of Istanbul. @@@ Results. IL-21 prevented the expansion of CD8(+)CD28(-) T cells stimulated by IL-15 by sus-taining CD28 expression at the mRNA level. IL-15 altered the expanded CD8(+)CD28(-) T cell memory subsets over the coculture duration, but the addition of IL-21 could change the subset distribution. In the presence of IL-15, the in vitro-expanded CD8(+)CD28(-) T cells were mainly intermediately differentiated cells, but they were mainly late differentiated cells in the presence of IL-21 plus IL-15. Moreover, IL-21 upregulated the expression of toxic molecules in the IL-15 -expanded CD8(+)CD28(-) T cells. @@@ Conclusions. IL-21 prevents IL-15-induced CD8(+)CD28(-) T cell amplification by downregu-lating CD28 at the transcriptional level. IL-21 can alter the subpopulation distribution and pheno-typic characteristics of CD8(+)CD28(-) T cells stimulated by IL-15.

• 单位
  南方医科大学; 广东省人民医院; 汕头大学