The tyrosine phosphatase CD45 regulates lymphopenia-induced T cell proliferation (47.15)

Abstract

Abstract Lymphopenia-induced T cell proliferation (LIP) occurs naturally in neonates and in patients with depleted T cell numbers due to infection or immunosuppression. LIP occurs in response to an interaction between TCR with self-MHC as well as to cytokines such as IL-7 and IL-15. However, the precise factors that induce and limit LIP are not well understood. CD45 is a leukocyte specific tyrosine phosphatase that reduces the TCR signaling threshold in T cells, modulates TLR signaling in dendritic cells and can negatively regulate cytokine signaling in leukocytes. Given that CD45 deficient mice have severely reduced numbers of T cells in the periphery, we sought to determine whether CD45 might regulate LIP. CD45 deficient mice were crossed with the RAG1 deficient mice to generate CD45RAG deficient mice and LIP was examined in a CD45 sufficient and CD45 deficient environment. LIP was significantly reduced in the spleen and lymph nodes of lymphopenic hosts lacking CD45. This was attributed to a reduced signal to induce T cell proliferation rather than increased cell death or delayed kinetics. Reduced levels of IL-7 but not IL-15 were evident in the spleens of CD45RAG1 deficient mice and CD45 deficient splenic dendritic cells were less efficient at stimulating antigen-induced T cell proliferation. Together this suggests that dendritic cell CD45 is required for optimal LIP and experiments are ongoing to evaluate this possibility.