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

EV Acosta-Rodriguez, L Rivino, J Geginat… - Nature …, 2007 - nature.com
Nature immunology, 2007nature.com
Abstract 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 …
Abstract
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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