ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Development of innate CD4+ and CD8+ T cells in Itk-deficient mice is regulated by distinct pathways.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Soquelitinib inhibition of IL-2-inducible T cell kinase ameliorates lung damage in murine models of systemic sclerosis.Arthritis research & therapy · 2025Article
- Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity.npj drug discovery · 2024Article
- Exploratory analysis of the key role of immune function changes in BPD.Pediatric discovery · 2024Article
- ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.Communications biology · 2022Article
- Interleukin-2-inducible T-cell kinase (Itk) signaling regulates potent noncanonical regulatory T cells.Clinical and translational medicine · 2021Article
- Signals for antigen-independent differentiation of memory CD8Cellular and molecular life sciences : CMLS · 2021Review
- Targeted Approaches to T-Cell Lymphoma.Journal of personalized medicine · 2021Review
- Tuning T helper cell differentiation by ITK.Biochemical Society transactions · 2020Review
- Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection AgainstFrontiers in immunology · 2019Article
- Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.PLoS pathogens · 2019Article
- T-Bet independent development of IFNγ secreting natural T helper 1 cell population in the absence of Itk.Scientific reports · 2017Article
- Phenotype of NK-Like CD8(+) T Cells with Innate Features in Humans and Their Relevance in Cancer Diseases.Frontiers in immunology · 2017Article
- PLZF(+) Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells.Molecules and cells · 2016Article
- Signaling in Effector Lymphocytes: Insights toward Safer Immunotherapy.Frontiers in immunology · 2016Review
- Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.Nature communications · 2015Article
- Itk signals promote neuroinflammation by regulating CD4+ T-cell activation and trafficking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia.OncoimmunologyArticle
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
T cell development in the thymus produces multiple lineages of cells, including innate T cells such as γδ 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 γδ 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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