IL-17-Producing Innate and Pathogen-Specific Tissue Resident Memory γδ T Cells Expand in the Lungs of Bordetella pertussis-Infected Mice

• Published in: The Journal of immunology (1950) Vol. 198; no. 1; pp. 363 - 374
• Main Authors: Misiak, Alicja, Wilk, Mieszko M, Raverdeau, Mathilde, Mills, Kingston H G
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.01.2017
• Subjects: Adaptive Immunity - immunology; Animals; Antigen-presenting cells; Antimicrobial peptides; Autoimmune diseases; Bacteria; Bordetella pertussis; Bordetella pertussis - immunology; CD103 antigen; CD69 antigen; Disease Models, Animal; Flow Cytometry; Immunity, Innate - immunology; Immunologic Memory - immunology; Immunological memory; Immunology; Infections; Interleukin 17; Interleukin-17 - biosynthesis; Interleukin-17 - immunology; Lungs; Lymphocytes; Lymphocytes T; Memory cells; Mice; Mice, Inbred C57BL; Mucosa; Mucosal immunity; Pathogens; Peptides; Pertussis; Receptors, Antigen, T-Cell, gamma-delta - immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Whooping cough; Whooping Cough - immunology; Whooping Cough - metabolism
• DOI: 10.4049/jimmunol.1601024
• ISSN: 0022-1767

γδ T cells play a role in protective immunity to infection at mucosal surface, but also mediate pathology in certain autoimmune diseases through innate IL-17 production. Recent reports have suggested that γδ T cells can have memory analogous to conventional αβ T cells. In this study we have examined the role of γδ T cells in immunity to the respiratory pathogen Bordetella pertussis γδ T cells, predominantly Vγ4 γ1 cells, produced IL-17 in the lungs as early as 2 h after infection. The bacterial burden during primary infection was significantly enhanced and the induction of antimicrobial peptides was reduced in the absence of early IL-17. A second peak of γδ T cells is detected in the lungs 7-14 d after challenge and these γδ T cells were pathogen specific. γδ T cells, exclusively Vγ4, from the lungs of infected but not naive mice produced IL-17 in response to heat-killed B. pertussis in the presence of APC. Furthermore, γδ T cells from the lungs of mice reinfected with B. pertussis produced significantly more IL-17 than γδ T cells from infected unprimed mice. γδ T cells with a tissue resident memory T cell phenotype (CD69 CD103 ) were expanded in the lungs during infection with B. pertussis and proliferated rapidly after rechallenge of convalescent mice. Our findings demonstrate that lung γδ T cells provide an early source of innate IL-17, which promotes antimicrobial peptide production, whereas pathogen-specific Vγ4 cells function in adaptive immunological memory against B. pertussis.