title: CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection.
abstract: Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4(+) T cells are important for the formation of functional lung-resident CD8(+) T cells after influenza virus infection. In the absence of CD4(+) T cells, CD8(+) T cells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8(+) T cells to the lung airways upon heterosubtypic challenge. CD4(+) T cell-derived interferon-γ was necessary for generating lung-resident CD103(+) CD8(+) Trm cells. Furthermore, expression of the transcription factor T-bet was increased in "unhelped" lung Trm cells, and a reduction in T-bet rescued CD103 expression in the absence of CD4(+) T cell help. Thus, CD4(+) T cell-dependent signals are important to limit expression of T-bet and allow for the development of CD103(+) CD8(+) Trm cells in the lung airways following respiratory infection.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Laidlaw
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
authors.forename: Nianzhi
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Marshall
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Staron
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Tianxia
authors.initials: T
authors.lastname: Guan
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cauley
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: joseph.craft@yale.edu.
authors.forename: Joe
authors.initials: J
authors.lastname: Craft
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA. Electronic address: susan.kaech@yale.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000096:biosynthesis*; D000098815:T-bet Transcription Factor
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C091367:alpha E integrins; D007371:Interferon-gamma