University of Massachusetts Medical School Faculty Publications

Title

The Tec kinase ITK regulates thymic expansion, emigration, and maturation of gammadelta NKT cells

UMMS Affiliation

Department of Pathology

Date

3-15-2013

Document Type

Article

Medical Subject Headings

Animals; Cell Aging; Cell Differentiation; Cell Migration Inhibition; Cell Movement; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural Killer T-Cells; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell, gamma-delta; Thymus Gland

Disciplines

Cell and Developmental Biology | Cell Biology | Developmental Biology | Immunity | Immunology and Infectious Disease

Abstract

The Tec family tyrosine kinase, Itk, regulates signaling downstream of the TCR. The absence of Itk in CD4(+) T cells results in impaired Th2 responses along with defects in maturation, cytokine production, and survival of iNKT cells. Paradoxically, Itk(-/-) mice have spontaneously elevated serum IgE levels, resulting from an expansion of the Vgamma1.1(+)Vdelta6.3(+) subset of gammadelta T cells, known as gammadelta NKT cells. Comparisons between gammadelta NKT cells and alphabeta iNKT cells showed convergence in the pattern of cell surface marker expression, cytokine profiles, and gene expression, suggesting that these two subsets of NKT cells undergo similar differentiation programs. Hepatic gammadelta NKT cells have an invariant TCR and are derived predominantly from fetal progenitors that expand in the thymus during the first weeks of life. The adult thymus contains these invariant gammadelta NKT cells plus a heterogeneous population of Vgamma1.1(+)Vdelta6.3(+) T cells with diverse CDR3 sequences. This latter population, normally excluded from the liver, escapes the thymus and homes to the liver when Itk is absent. In addition, Itk(-/-) gammadelta NKT cells persistently express high levels of Zbtb16 (PLZF) and Il4, genes that are normally downregulated in the most mature subsets of NKT cells. These data indicate that Itk signaling is required to prevent the expansion of gammadelta NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation.

Rights and Permissions

Citation: J Immunol. 2013 Mar 15;190(6):2659-69. doi: 10.4049/jimmunol.1202531. Link to article on publisher's site

Comments

Co-author Amanda Prince is a student in the Immunology and Virology Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

Keywords

UMCCTS funding

PubMed ID

23378428