Title

Development of innate CD4+ and CD8+ T cells in Itk-deficient mice is regulated by distinct pathways

Student Author(s)

Amanda L. Prince

Academic Program

Immunology & Microbiology

UMMS Affiliation

Department of Pathology

Publication Date

2014-07-15

Document Type

Article

Disciplines

Immunology and Infectious Disease | Immunology of Infectious Disease | Immunopathology

Abstract

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.

DOI of Published Version

10.4049/jimmunol.1302059

Source

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

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

Related Resources

Link to Article in PubMed

PubMed ID

24943215

Link to Full Text

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