Friday, April 19, 2024
4/19/2024
PROJECT SUMMARY Memory T cells rapidly and efficiently respond upon re-encountering pathogens, thanks to the existence of a diverse set of memory T cells with different migratory properties and functional capabilities. Memory CD8+ T cells can be broadly divided into 3 subsets: 2 highly mobile circulating memory CD8+ T cell subsets, termed central and effector memory T cells and a memory T cell pool that is resident in non- lymphoid tissues. The mechanisms that regulate this heterogeneity in the memory pool and whether these subsets are interdependent, or the generation of a specific memory population can be manipulated to the advantage of the host remain unknown in the field. Our preliminary data supports that the latter is possible and provides evidence for a critical role of NFkB signaling regulating T cell subset memory diversity. We will use novel inducible mouse models able to regulate the strength of NFkB signaling to mechanistically define how NFkB signals regulate resident and central memory generation and maintenance in the context of influenza infection (Aim 1). In Aim 2, we will employ different loss and gain of function models to determine how Pim1K, a novel downstream intermediate of NFkB signals in T cells, regulates T cell memory subset diversity. We anticipate that the information resulting from the studies proposed here will be highly significant. Data from these studies will advance the field of T cell memory where it is still unclear how each of the T cell memory subsets is regulated. Additionally, we expect that our results will provide with novel and critical avenues that will permit us to tune the generation of resident memory T cells in barrier tissues for the advantage of the host. This may be especially relevant for influenza infection and vaccination where TRM longevity is specially limited and critical for heterosubtypic immunity to IAV.
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