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

Jianfang Hu, Avery August

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The Tec family kinase Ilk 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 CD62LlowCD44 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-γ and are able to produce IFN-γ directly ex vivo in response to stimulation. Itk deficiency greatly decreases the number of CD4+ T cells with CD62LhighCD44 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 highCD44low "naive" CD4+ and CD62LlOWCD44high "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 +CD62LlOWCD44high memory phenotype T cells have innate immune function.

Original languageEnglish (US)
Pages (from-to)6544-6552
Number of pages9
JournalJournal of Immunology
Volume180
Issue number10
DOIs
StatePublished - Jan 1 2008

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T-Lymphocytes
Phenotype
Interleukin-18
Listeria monocytogenes
Cell Lineage
Interleukin-12
Thymus Gland
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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abstract = "The Tec family kinase Ilk 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 CD62LlowCD44 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-γ and are able to produce IFN-γ directly ex vivo in response to stimulation. Itk deficiency greatly decreases the number of CD4+ T cells with CD62LhighCD44 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 highCD44low {"}naive{"} CD4+ and CD62LlOWCD44high {"}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 +CD62LlOWCD44high memory phenotype T cells have innate immune function.",
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Naive and innate memory phenotype CD4+ T cells have different requirements for active Itk for their development. / Hu, Jianfang; August, Avery.

In: Journal of Immunology, Vol. 180, No. 10, 01.01.2008, p. 6544-6552.

Research output: Contribution to journalArticle

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