Naive and innate memory phenotype CD4+ T cells have different requirements for active Itk for their development.
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.
Hu
Jianfang
J
Center for Molecular Immunology and Infectious Disease and Department of Veterinary & Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
August
Avery
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology
D018960:Hyaluronan Receptors; D019041:L-Selectin; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase