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

Abstract

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. 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. IL-21 prevented the expansion of CD8+CD28- T cells stimulated by IL-15 by sustaining 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. IL-21 prevents IL-15-induced CD8+CD28- T cell amplification by downregulating CD28 at the transcriptional level. IL-21 can alter the subpopulation distribution and phenotypic characteristics of CD8+CD28- T cells stimulated by IL-15.