Innate PLZF+CD4+ alphabeta T cells develop and expand in the absence of Itk
Immunology & Microbiology
Department of Pathology
Medical Subject Headings
Animals; Antigens, CD1d; CD4-Positive T-Lymphocytes; Cell Differentiation; *Cell Proliferation; Cells, Cultured; Flow Cytometry; Gene Expression; H-2 Antigens; Interleukin-4; Kruppel-Like Transcription Factors; Lymph Nodes; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell, alpha-beta; Reverse Transcriptase Polymerase Chain Reaction; Spleen; T-Lymphocyte Subsets; Thymocytes; beta 2-Microglobulin
T cell development in the thymus produces multiple lineages of cells, including innate T cells. Studies in mice harboring alterations in TCR signaling proteins or transcriptional regulators have revealed an expanded population of CD4(+) innate T cells in the thymus that produce IL-4 and express the transcription factor promyelocytic leukemia zinc finger (PLZF). In these mice, IL-4 produced by the CD4(+)PLZF(+) T cell population leads to the conversion of conventional CD8(+) thymocytes into innate CD8(+) T cells resembling memory T cells expressing eomesodermin. The expression of PLZF, the signature invariant NKT cell transcription factor, in these innate CD4(+) T cells suggests that they might be a subset of alphabeta or gammadelta TCR(+) NKT cells or mucosal-associated invariant T (MAIT) cells. To address these possibilities, we characterized the CD4(+)PLZF(+) innate T cells in itk(-/-) mice. We show that itk(-/-) innate PLZF(+)CD4(+) T cells are not CD1d-dependent NKT cells, MR1-dependent MAIT cells, or gammadelta T cells. Furthermore, although the itk(-/-) innate PLZF(+)CD4(+) T cells express alphabeta TCRs, neither beta2-microglobulin-dependent MHC class I nor any MHC class II molecules are required for their development. In contrast to invariant NKT cells and MAIT cells, this population has a highly diverse TCRalpha-chain repertoire. Analysis of peripheral tissues indicates that itk(-/-) innate PLZF(+)CD4(+) T cells preferentially home to spleen and mesenteric lymph nodes owing to increased expression of gut-homing receptors, and that their expansion is regulated by commensal gut flora. These data support the conclusion that itk(-/-) innate PLZF(+)CD4(+) T cells are a novel subset of innate T cells.
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Citation: J Immunol. 2014 Jul 15;193(2):673-87. doi: 10.4049/jimmunol.1302058. Epub 2014 Jun 13. Link to article on publisher's site
DOI of Published Version
Journal of immunology (Baltimore, Md. : 1950)
Prince, Amanda L.; Watkin, Levi B.; Yin, Catherine C.; Selin, Liisa K.; Kang, Joonso; Schwartzberg, Pamela L.; and Berg, Leslie J., "Innate PLZF+CD4+ alphabeta T cells develop and expand in the absence of Itk" (2014). GSBS Student Publications. 1924.