Interleukin 17 (IL-17)–producing T helper cells (TH-17 cells) have been characterized in mice as a distinct subset of effector cells, but their identity and properties in humans remain elusive. We report here that expression of CCR6 and CCR4 together identified human memory CD4+ T cells selectively producing IL-17 and expressing mRNA encoding the human ortholog of mouse RORγt, a transcription factor, whereas CCR6 and CXCR3 identified TH1 cells producing interferon-γ and T helper cells producing both interferon-γ and IL-17. Memory T cells specific for Candida albicans were present mainly in the CCR6+CCR4+ TH-17 subset, whereas memory T cells specific for Mycobacterium tuberculosis were present in CCR6+CXCR3+ T helper type 1 subset. The elicitation of IL-17 responses correlated with the capacity of C. albicans hyphae to stimulate antigen-presenting cells for the priming of TH-17 responses in vitro and for the production of IL-23 but not IL-12. Our results demonstrate that human TH-17 cells have distinct migratory capacity and antigenic specificities and establish a link between microbial products, T helper cell differentiation and homing in response to fungal antigens.
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We thank M. Messi for help with initial experiments, and M. Manz and M. Uguccioni for critical reading and comments. Anti-α4β7 (Act1) was from C.R. Mackay (The Garvan institute). Supported by the Swiss National Science Foundation (31-101962 to F.S. and 31-112678 to A.L.), the European Commission FP6 Programme (LSHP-CT-2003-503240 (Mucosal Vaccines for Poverty-Related Diseases); LSB-CT-2005-518167 (Innovative Chemokine-Based Therapeutic Strategies for Autoimmunity and Chronic Inflammation)), the National Institutes of Health (U19 AI057266-01) and the Helmut Horten Foundation (for The Institute for Research in Biomedicine).
The authors declare no competing financial interests.
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