Development of innate CD4+ and CD8+ T cells in Itk-deficient mice is regulated by distinct pathways
Immunology & Microbiology
Department of Pathology
Medical Subject Headings
Animals; Antigens, CD1d; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Proliferation; Flow Cytometry; Interleukin-15; Interleukin-4; Kruppel-Like Transcription Factors; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural Killer T-Cells; Protein-Tyrosine Kinases; Rats; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; T-Box Domain Proteins; Thymocytes
Immunology and Infectious Disease | Immunology of Infectious Disease | Immunopathology
T cell development in the thymus produces multiple lineages of cells, including innate T cells such as gammadelta TCR(+) cells, invariant NKT cells, mucosal-associated invariant T cells, and H2-M3-specific cells. Although innate cells are generally a minor subset of thymocytes, in several strains of mice harboring mutations in T cell signaling proteins or transcriptional regulators, conventional CD8(+) T cells develop as innate cells with characteristics of memory T cells. Thus, in Itk-deficient mice, mature CD4(-)CD8(+) (CD8 single-positive [SP]) thymocytes express high levels of the transcription factor eomesodermin (Eomes) and are dependent on IL-4 being produced in the thymic environment by a poorly characterized subset of CD4(+) thymocytes expressing the transcriptional regulator promyelocytic leukemia zinc finger. In this study, we show that a sizeable proportion of mature CD4(+)CD8(-) (CD4SP) thymocytes in itk(-/-) mice also develop as innate Eomes-expressing T cells. These cells are dependent on MHC class II and IL-4 signaling for their development, indicating that they are conventional CD4(+) T cells that have been converted to an innate phenotype. Surprisingly, neither CD4SP nor CD8SP innate Eomes(+) thymocytes in itk(-/-) or SLP-76(Y145F) mice are dependent on gammadelta T cells for their development. Instead, we find that the predominant population of Eomes(+) innate itk(-/-) CD4SP thymocytes is largely absent in mice lacking CD1d-specific invariant NKT cells, with no effect on innate itk(-/-) CD8SP thymocytes. In contrast, both subsets of innate Eomes(+)itk(-/-) T cells require the presence of a novel promyelocytic leukemia zinc finger-expressing, SLAM family receptor adapter protein-dependent thymocyte population that is essential for the conversion of conventional CD4(+) and CD8(+) T cells into innate T cells with a memory phenotype.
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Citation: J Immunol. 2014 Jul 15;193(2):688-99. doi: 10.4049/jimmunol.1302059. Epub 2014 Jun 18. Link to article on publisher's site
DOI of Published Version
Journal of immunology (Baltimore, Md. : 1950)
Prince, Amanda L.; Kraus, Zachary; Carty, Shannon A.; Ng, Caleb; Yin, Catherine C.; Jordan, Martha S.; Schwartzberg, Pamela L.; and Berg, Leslie J., "Development of innate CD4+ and CD8+ T cells in Itk-deficient mice is regulated by distinct pathways" (2014). GSBS Student Publications. 1913.