Unknown

Dataset Information

0

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


ABSTRACT: T cell development in the thymus produces multiple lineages of cells, including innate T cells such as ?? 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 ?? 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.

SUBMITTER: Prince AL 

PROVIDER: S-EPMC4114307 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Prince Amanda L AL   Kraus Zachary Z   Carty Shannon A SA   Ng Caleb C   Yin Catherine C CC   Jordan Martha S MS   Schwartzberg Pamela L PL   Berg Leslie J LJ  

Journal of immunology (Baltimore, Md. : 1950) 20140618 2


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, m  ...[more]

Similar Datasets

| S-EPMC2689280 | biostudies-literature
2009-05-20 | GSE12466 | GEO
2009-05-29 | E-GEOD-12466 | biostudies-arrayexpress
| S-EPMC4083617 | biostudies-literature
| S-EPMC1567699 | biostudies-literature
| S-EPMC4033297 | biostudies-literature
| S-EPMC5214944 | biostudies-literature
| S-EPMC3731786 | biostudies-literature
2021-10-19 | GSE185327 | GEO
2011-12-20 | GSE28200 | GEO