Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response.
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.
Scriba
Thomas J
TJ
South African Tuberculosis Vaccine Initiative, Observatory, South Africa. thomas.scriba@uct.ac.za
Kalsdorf
Barbara
B
Abrahams
Deborah-Ann
DA
Isaacs
Fatima
F
Hofmeister
Jessica
J
Black
Gillian
G
Hassan
Hisham Y
HY
Wilkinson
Robert J
RJ
Walzl
Gerhard
G
Gelderbloem
Sebastian J
SJ
Mahomed
Hassan
H
Hussey
Gregory D
GD
Hanekom
Willem A
WA
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
D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22