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

ABSTRACT 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 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. Conclusions 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.