title: Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response.
abstract: We investigated whether the proinflammatory T cell cytokines IL-17 and IL-22 are induced by human mycobacterial infection. Remarkably, >20% of specific cytokine-producing CD4(+) T cells in peripheral blood of healthy, mycobacteria-exposed adults expressed IL-17 or IL-22. Specific IL-17- and IL-22-producing CD4(+) T cells were distinct from each other and from Th1 cytokine-producing cells. These cells had phenotypic characteristics of long-lived central memory cells. In patients with tuberculosis disease, peripheral blood frequencies of these cells were reduced, whereas bronchoalveolar lavage fluid contained higher levels of IL-22 protein compared with healthy controls. IL-17 was not detected in this fluid, which may be due to suppression by Th1 cytokines, as PBMC IL-17 production was inhibited by IFN-gamma in vitro. However, Th1 cytokines had no effect on IL-22 production in vitro. Our results imply that the magnitude and complexity of the anti-mycobacterial immune response have historically been underestimated. IL-17- and IL-22-producing CD4(+) T cells may play important roles in the human immune response to mycobacteria.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Observatory, South Africa. thomas.scriba@uct.ac.za
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Barbara
authors.initials: B
authors.lastname: Kalsdorf
authors.forename: Deborah-Ann
authors.initials: DA
authors.lastname: Abrahams
authors.forename: Fatima
authors.initials: F
authors.lastname: Isaacs
authors.forename: Jessica
authors.initials: J
authors.lastname: Hofmeister
authors.forename: Gillian
authors.initials: G
authors.lastname: Black
authors.forename: Hisham Y
authors.initials: HY
authors.lastname: Hassan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Gelderbloem
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000032:analysis / Q000378:metabolism*; D007378:Interleukins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22