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* South African Tuberculosis Vaccine Initiative and
Mycobacterial Immunology Group, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town;
Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Stellenbosch, South Africa;
Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany;
¶ Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan;
|| Wellcome Trust Centre for Clinical Tropical Medicine, Division of Medicine, Imperial College; and
# National Institute for Medical Research, The Ridgeway, London, United Kingdom
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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Aeras Global Tuberculosis Vaccine Foundation (to W.A.H., G.D.H., and H.M.). T.J.S. is a Wellcome Trust Research Training Fellow (080929/Z/06/Z). W.A.H. is supported by the National Institutes of Health (Grants RO1AI065653 and NO1AI70022), as is G.D.H. (Grant D43TW007115). W.A.H. is also supported by the Dana Foundation, the Bill and Melinda Gates Foundation through Grand Challenges in Global Health Grants 37772 and 37885, and the European and Developing Countries Trials Partnership. B.K. is supported by the German National Respiratory Society and Foundation (DGP) and the German Research Foundation (DFG SCHE 1556). G.W. is supported by a Grand Challenges in Global Health Grant GC6-74. R.J.W. is supported by the Wellcome Trust and U.K. Medical Research Council.
2 Address correspondence and reprint requests to Dr. Thomas J. Scriba, South African Tuberculosis Vaccine Initiative, Werner and Beit Building, Anzio Road, Observatory 7800, South Africa. E-mail address: thomas.scriba{at}uct.ac.za
3 Abbreviations used in this paper: Mtb, Mycobacterium tuberculosis; TB, tuberculosis; BCG, bacillus Calmette-Guérin; BAL, bronchoalveolar lavage; BALF, BAL fluid; PPD, purified protein derivative; ESTA-6, early secretory antigenic target-6; CFP-10, culture filtrate protein-10; SEB, staphylococcal enterotoxin B; PTB, pulmonary TB.
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