title: Interleukin-7, but not thymic stromal lymphopoietin, plays a key role in the T cell response to influenza A virus.
abstract: The immune response to viral infection is ideally rapid and specific, resulting in viral clearance and establishment of immune memory. Some viruses such as HIV can evade such responses leading to chronic infection, while others like Influenza A can elicit a severe inflammatory response with immune-related complications including death. Cytokines play a major role in shaping the appropriate outcomes to infection. While Interleukin-7 (IL-7) has a critical role in T and B cell development, treatment with IL-7 has recently been shown to aid the adaptive T cell response in clearance of chronic viral infection. In contrast, the IL-7-related cytokine thymic stromal lymphopoietin (TSLP) has a limited role in lymphocyte development but is important in the immune response to parasitic worms and allergens. The role for these cytokines in the immune response to an acute viral infection is unclear. IL-7 and TSLP share IL-7Rα as part of their heterodimeric receptors with the gamma common chain (γc) and TSLPR, respectively. We investigated the role of IL-7 and TSLP in the primary immune response to influenza A infection using hypomorphic IL-7Rα (IL-7Rα(449F)) and TSLPR(-/-) mice. We found that IL-7, but not TSLP, plays an important role in control of influenza A virus. We also showed that IL-7 signaling was necessary for the generation of a robust influenza A-specific CD4 and CD8 T cell response and that this requirement is intrinsic to CD8 T cells. These findings demonstrate a significant role for IL-7 during acute viral infection.
authors.affiliation: Infection, Inflammation and Immunity Research Group, Department of Microbiology & Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Plumb
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Patton
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Seo
authors.forename: Emma-Kate
authors.initials: EK
authors.lastname: Loveday
authors.forename: François
authors.initials: F
authors.lastname: Jean
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Ninan
authors.initials: N
authors.lastname: Abraham
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D015851:Interleukin-7 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D015851:Interleukin-7; D054367:Receptors, CXCR3; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; C410591:Tslpr protein, mouse; C415350:interleukin-7 receptor, alpha chain; D000094632:Thymic Stromal Lymphopoietin