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Publication : Naive and innate memory phenotype CD4+ T cells have different requirements for active Itk for their development.

First Author  Hu J Year  2008
Journal  J Immunol Volume  180
Issue  10 Pages  6544-52
PubMed ID  18453573 Mgi Jnum  J:134960
Mgi Id  MGI:3790153 Doi  10.4049/jimmunol.180.10.6544
Citation  Hu J, et al. (2008) Naive and innate memory phenotype CD4+ T cells have different requirements for active Itk for their development. J Immunol 180(10):6544-52
abstractText  The Tec family kinase Itk regulates the development of conventional and innate CD8(+) T cells. However, little is known about the role of Itk in the development of CD4(+) T cell lineages, although the role of Itk in the T cell activation and function is well defined. We show in this study that Itk null mice have increased percentage of CD62L(low)CD44(high) memory phenotype CD4(+) T cells compared with wild-type mice. These cells arise directly in the thymus, express high levels of transcripts for the T-bet and IFN-gamma and are able to produce IFN-gamma directly ex vivo in response to stimulation. Itk deficiency greatly decreases the number of CD4(+) T cells with CD62L(high)CD44(low) naive phenotype, but has no effect on the number of memory phenotype CD4(+) T cells, indicating that the development of memory phenotype CD4(+) T cells is Itk-independent. We further show that the development of the naive phenotype CD4(+) T cells is dependent on active Itk signals and can be rescued by expression of Itk specifically in T cells. Our data also show that Itk is required for functional TCR signaling in these cells, but not for the innate function in response to IL-12/IL-18 or Listeria monocytogenes stimulation. These results indicate that CD62L(high)CD44(low) 'naive' CD4(+) and CD62L(low)CD44(high) 'innate memory phenotype' CD4(+) T cells may be independent populations that differ in their requirement for Itk signals for development. Our data also suggest that CD4(+)CD62L(low)CD44(high) memory phenotype T cells have innate immune function.
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