T Cell Factor-1 and beta-catenin regulate the development of memory-like CD8 thymocytes (110.6)

Abstract

Abstract In addition to conventional alpha-beta T cells, recent studies have demonstrated the presence of a subset of CD8 single positive (SP) mature thymocytes, referred to as memory-like or innate-like thymocytes that acquire effector functions in the thymus as a result of the maturation process. These cells have been described in mice with mutations in KLF2, Itk, CBP genes and SLAM family members and in non-mutant Balb/c mice in response to IL-4 produced by thymocytes. Here, we demonstrate that enhanced function of transcription factors T Cell Factor (TCF)-1 and beta-catenin regulate the frequency of IL-4 producing thymocytes that promote the generation of Eomes-expressing memory-like CD8 thymocytes in trans. By contrast, TCF1-deficient mice show a paucity of these cells demonstrating an essential requirement of TCF1 for the generation of Eomes-expressing memory-like CD8 thymocytes. Generation of TCF1 and beta-catenin-dependent memory-like CD8 thymocytes requires the expression of IL-4 and IL-4 receptor. CD8 memory-like T cells migrate to the periphery and are functional. Thus, TCF1 and beta-catenin regulate the generation of memory-like CD8 T cells in the thymus in a non-cell intrinsic manner.