title: The tyrosine kinase Itk suppresses CD8+ memory T cell development in response to bacterial infection.
abstract: Vaccine efficacy depends on strong long-term development of immune memory and the formation of memory CD8(+) T cells is critical for recall responses to infection. Upon antigen recognition by naïve T cells, the strength of the TcR signal influences the subsequent effector and memory cells differentiation. Here, we have examined the role of Itk, a tyrosine kinase critical for TcR signaling, in CD8(+) effector and memory T cell differentiation during Listeria monocytogenes infection. We found that the reduced TcR signal strength in Itk deficient naïve CD8(+) T cells enhances the generation of memory T cells during infection. This is accompanied by increased early Eomesodermin, IL-7Rα expression and memory precursor effector cells. Furthermore, Itk is required for optimal cytokine production in responding primary effector cells, but not secondary memory responses. Our data suggests that Itk-mediated signals control the expression of Eomesodermin and IL-7Rα, thus regulating the development of memory CD8(+) T cells, but not subsequent response of memory cells.
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Weishan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Jessica
authors.initials: J
authors.lastname: Briggs
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Tina
authors.initials: T
authors.lastname: Chew
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Simrita
authors.initials: S
authors.lastname: Deol
authors.affiliation: Department of Microbiology &Immunology, Cornell University, Ithaca, NY, 14853.
authors.forename: Avery
authors.initials: A
authors.lastname: August
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; C491198:Eomes protein, mouse; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D020825:T-Box Domain Proteins; C415350:interleukin-7 receptor, alpha chain; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase