Characterization of IL-15 independent memory CD8 T cell subsets (P1438)

Abstract

Abstract IL-15 is required for the maintenance and homeostatic proliferation of conventionally characterized memory CD8 T cells, and thus sets a carrying capacity for the size of the memory CD8 T cell compartment. However, we recently demonstrated that heterologous prime boost (HPB) vaccine regimens that establish very abundant memory CD8 T cell populations result in an enlargement of the memory CD8 compartment, which is almost entirely due to the addition of vaccine-specific memory T cells that lack CD62L expression. Here, we test the hypothesis that memory CD8 T cells resulting from HPB are less dependent on IL-15. We demonstrate that boosted memory cells express decreased levels of IL15Rβ and undergo little homeostatic proliferation. When co-transferring primary and boosted memory CD8 T cells into IL15KOs, boosted memory CD8 T cells that lacked CD62L expression were better able to persist compared to primary memory CD8 T cells (regardless of CD62L expression). We extended these studies by demonstrating that primary memory CD8 T cells that are resident in several peripheral tissues were also maintained in the absence of IL-15, and in some cases, exhibited IL-15 independent homeostatic proliferation. These observations point to a distinct lineage, not wholly defined by lack of CD62L expression, that harbors less dependence on IL-15 for maintenance. This has ramifications for regulation of memory CD8 T cell quantity following certain vaccine modalities and at front line tissues.