The timing of stimulation and IL-2 signaling regulate secondary CD8 T cell responses (LYM5P.701)

Abstract

Abstract Memory CD8 T cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. While parameters influencing the generation of primary (1o) CD8 T cells are well established, the factors controlling the development of secondary (2o) CD8 T cell responses remain largely unknown. Here, we explored the mechanisms involved in the generation and development of 2o memory (M) CD8 T cells. We observed that the time at which 1o M CD8 T cells recognize Ag and become activated impacts their fate and differentiation into 2o M CD8 T cells. Late-entry of 1o M CD8 T cells into an immune response not only facilitated the expression of transcription factors associated with memory formation in 2o effector CD8 T cells, but also influenced the ability of 2o M CD8 T cells to localize within the LN, produce IL-2, and undergo Ag-driven proliferation. The timing of stimulation of 1o M CD8 T cells also impacted the duration of expression of the high-affinity IL-2 receptor (CD25) on 2o effector CD8 T cells and their sensitivity to IL-2 signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2o CD8 T cells, we confirmed the role of IL-2 in controlling the differentiation of 2o CD8 T cell responses. Thus, our data suggest that the process of 1o M to 2o M CD8 T cell differentiation is not fixed and can be manipulated, a notion with relevance for the design of future prime-boost vaccination approaches.