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

Abstract

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; CD44(hi)CD122(+)) 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.

• Authors: Weishan Huang, Fei Huang, Arun Kumar Kannan, Jianfang Hu, Avery August
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 96 Issue 1 Pg. 55-63 (Jul 2014) ISSN: 1938-3673 [Electronic] United States
• PMID: 24620029 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2014 Society for Leukocyte Biology.

Chemical References

• Receptors, Antigen, T-Cell, gamma-delta
• STAT6 Transcription Factor
• Stat6 protein, mouse
• Interleukin-4
• Protein-Tyrosine Kinases
• emt protein-tyrosine kinase

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Immunity, Innate
• Immunologic Memory
• Infections (genetics, immunology)
• Interleukin-4 (genetics, immunology)
• Mice
• Mice, Knockout
• Models, Immunological
• Natural Killer T-Cells (immunology)
• Protein-Tyrosine Kinases (immunology)
• Receptors, Antigen, T-Cell, gamma-delta (genetics, immunology)
• STAT6 Transcription Factor (genetics, immunology)
• Signal Transduction (genetics, immunology)