α-GalCer administration expands virtual memory CD8 +T cells through IL-4 secretion

Abstract

Abstract Virtual memory CD8 +T (CD8 +T VM) cells, a unique subset of CD8 +T cells bearing memory phenotypes, exist in naïve and even in germ-free mice. Distinct from the conventional memory T cells, T VMcells are antigen-inexperienced but able to respond quickly in a cognate antigen-independent manner, thus could provide a broad range of innate-like protective effects. Our previous study showed that T VMcells could be expanded by type 2/interleukin-4 (IL-4) responses. Thus, we used α-galactosylceramide (α-GalCer) to selectively activate invariant natural killer T (iNKT) cells and create a type 2/IL-4 response, which in turn induced robust T VMcell expansion. We further demonstrated that CD1d molecule and NKT cells were necessary for α-GalCer-induced T VMcell expansion, but the T VMcell expansion was only partially dependent on IL-4 in this scenario. It remains unclear how IL-4 induces T VMcell expansion, and what other cytokine(s) may contribute to IL-4-independent T VMcell expansion upon α-GalCer treatment. Among multiple cytokines induced by α-GalCer treatment, we found that in addition to IL-4, IL-15 and type I interferons (IFNs), which have been reported to participate in the development and expansion of T VMcells, were elevated in response to α-GalCer treatment in vivo. We further found that IL-4 and IL-15 but not type I IFNs drove T VMcell proliferation and expansion in vitro. Thus. we speculated that one of the factors that involves in IL-4-independent α-GalCer-induced T VMcell expansion may be IL-15. We are currently testing this hypothesis. Taken together, our results suggested that the activation of iNKT cells by α-GalCer expands T VMcell pool through IL-4 production, thus may regulate the ability of T VMcells to provide broad protection. Supported by grants from MOST (109-2320-B-002-074-MY3), NHRI (EX110/111-11033SI) and NTU (111L7829), Taiwan