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The Tec kinase ITK regulates thymic expansion, emigration, and maturation of γδ NKT cells1
Ist Teil von
The Journal of immunology (1950), 2013-02, Vol.190 (6), p.2659-2669
Erscheinungsjahr
2013
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
The Tec family tyrosine kinase, Itk, regulates signaling downstream of the T cell receptor (TCR). The absence of Itk in CD4
+
T cells results in impaired Th2 responses along with defects in maturation, cytokine production and survival of
i
NKT cells. Paradoxically,
Itk
−/−
mice have spontaneously elevated serum IgE levels, resulting from an expansion of the Vγ1.1
+
Vδ6.3
+
subset of γδ T cells, known as γδ NKT cells. Comparisons between γδ NKT cells and αβ
i
NKT 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 γδ 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 γδ NKT cells plus a heterogeneous population of Vγ1.1
+
Vδ6.3
+
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
−/−
γδ NKT cells persistently express high levels of
Zbtb16
(PLZF) and
Il4
, genes that are normally down-regulated in the most mature subsets of NKT cells. These data indicate that Itk signaling is required to prevent the expansion of γδ NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation.