Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells

Interleukin 17 (IL-17)-producing T helper cells (T_H-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 T_H1 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⁺ T_H-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 T_H-17 responses in vitro and for the production of IL-23 but not IL-12. Our results demonstrate that human T_H-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.