ITK tunes IL-4-induced development of innate memory CD8+ T cells in a γδ T and invariant NKT cell-independent manner

Weishan Huang, Fei Huang, Arun Kumar Kannan, Jianfang Hu, Avery August

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10 Scopus citations


True memory CD8++ T cells develop post antigenic exposure and can provide life-long immune protection. More recently, other types of memory CD8++ T cells have been described, such as the memory-like CD8+ T cells (IMP; CD44hiCD122+) that arise spontaneously in Itk-/- mice, which are suggested to develop as a result of IL-4 secreted by NKT-like γδ T or PLZF+ NKT cells found in Itk-/- mice. However, we report here that whereas IMP CD8+ T cell development in Itk-/- mice is dependent on IL-4/STAT6 signaling, it is not dependent on any γδ T or iNKT cells. Our experiments suggest that the IMP develops as a result of tuning of the CD8+ T cell response to exogenous IL-4 and TCR triggering by ITK and challenge the current model of IMP CD8+ T cell development as a result of NKT-like γδ T or iNKT cells. These findings suggest that some naive CD8+ T cells may be preprogrammed by weak homeostatic TCR signals in the presence of IL-4 to become memory phenotype cells with the ability to elaborate effector function rapidly. The role of ITK in this process suggests a mechanism by which IMP CD8+ T cells can be generated rapidly in response to infection.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalJournal of Leukocyte Biology
Issue number1
Publication statusPublished - Jul 2014


All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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