Enhanced development of memory like CD8 T cells with innate immune function in the absence of Tec kinase signals (87.26)

Abstract

Abstract T cells with a memory phenotype and innate immune function have been reported, but the signals regulating these cells are still unclear. The Tec family kinases are highly expressed in T cells and involved in T cell activation and differentiation. We show here that Itk null mice have a consistent increase in the proportions and absolute numbers of CD8+ T cells that have memory phenotype (CD8+ CD44highCD122high). This elevation is observed in mice carrying an Itk mutant lacking the kinase domain, but not in mice carrying a transgene of the related kinase Rlk/Txk, which indicates that active Tec kinase signaling suppresses their presence. These cells carry preformed message for IFN-gamma and are able to produce IFN-gamma directly ex vivo. They also carry abundant transcripts for Granzyme B and eomesodermin. We also show that memory phenotype CD8+ T cells rapidly secrete IFN-gamma after infection with Listeria monocytogenes (LM) and Itk null mice have the ability to effectively response to infection. Antibody-mediated depletion of CD8+ T cells resulted in significantly reduced ability to clear LM infection in both WT and Itk null mice. Furthermore, transfer of small number of memory phenotype CD8+ T cells can reduce bacterial counts in IFN-gamma deficient mice 3 days after LM infection. These results indicate that these cells are functional CD8+CD44+ cells with innate like function and that the active signals from Tec kinases regulate their development.