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 RORgammat, a transcription factor, whereas CCR6 and CXCR3 identified T(H)1 cells producing interferon-gamma and T helper cells producing both interferon-gamma 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.
Acosta-Rodriguez
Eva V
EV
Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
Rivino
Laura
L
Geginat
Jens
J
Jarrossay
David
D
Gattorno
Marco
M
Lanzavecchia
Antonio
A
Sallusto
Federica
F
Napolitani
Giorgio
G
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000096:biosynthesis; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; C515354:CCR4 protein, human; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; C515355:Ccr4 protein, mouse; C515188:Cxcr3 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse