Title

The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Pathology

Date

7-25-2006

Document Type

Article

Medical Subject Headings

Animals; Animals, Newborn; Antigens, CD44; CD8-Positive T-Lymphocytes; *Cell Differentiation; Cell Proliferation; Cells, Cultured; Immunologic Memory; Interleukin-15; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell; T-Box Domain Proteins; Thymus Gland; Time Factors; Up-Regulation; Xenopus Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The Tec family tyrosine kinases, Itk and Rlk, are expressed in thymocytes and peripheral T cells and regulate thresholds of T cell receptor signaling. Yet little is known about the specific role of Itk- and Rlk-dependent signals in CD8(+) T cell maturation. We show here that Itk(-/-) and Rlk(-/-)Itk(-/-) mice were nearly devoid of conventional CD8(+) T cells and, instead, contained a large population of CD8(+) T cells that bear striking similarity to lineages of innate lymphocytes. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes and T cells were CD44(hi), CD122(+), and NK1.1(+); were able to produce interferon-gamma directly ex vivo; and were dependent on interleukin-15. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes expressed abundant transcripts for the T box transcription factor, eomesodermin, correlating with their phenotype and function. These data indicate a critical role for Itk and Rlk in conventional CD8(+) T cell development in the thymus.

Rights and Permissions

Citation: Immunity. 2006 Jul;25(1):79-91. Link to article on publisher's site

Related Resources

Link to article in PubMed

PubMed ID

16860759