title: 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.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Weishan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Kannan
authors.affiliation: Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA; and Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pennsylvania, USA averyaugust@cornell.edu.
authors.forename: Avery
authors.initials: A
authors.lastname: August
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007113:Immunity, Innate; D007156:Immunologic Memory; D007239:Infections / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D055611:Natural Killer T-Cells / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase
keywords: IFN-γ; T cell memory differentiation; eomesodermin; nonconventional T cells; phenotype