Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types

DC subsets and macrophages differentially mediate memory CD8 T cell maintenance via IL‐15 transpresentation and CD70/CD27 interactions. This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL‐15. Although DCs support IL‐15‐mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL‐15 on memory CD8 T cells, all in vitro‐derived or ex vivo‐isolated DCs maintained CD8 T cells better than rIL‐15 alone, and FLT‐3L‐DCs are the most efficient compared with GM‐DCs, BM‐derived macrophages, or freshly isolated DCs. Although FLT‐3L‐DCs were the least effective at inducing CD8 T cell proliferation, FLT‐3L‐DCs promoted better CD8 T cell survival and increased Bcl‐2 and MCL‐2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL‐15Rα and IL‐15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL‐15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN‐α enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL‐15 trans‐presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently.