Human Th17 cells comprise heterogeneous subsets including IFN-gamma-producing cells with distinct properties from the Th1 lineage.
Th17 cells have been named after their signature cytokine IL-17 and accumulating evidence indicates their involvement in the induction and progression of inflammatory diseases. In addition to IL-17 single-producing T cells, IL-17/IFN-gamma double-positive T cells are found in significantly elevated numbers in inflamed tissues or blood from patients with chronic inflammatory disorders. Because IFN-gamma is the classical Th1-associated cytokine, the origin and roles of these subsets remain elusive. In this paper, we show that not only IL-17(+)/IFN-gamma(+) but also IFN-gamma(+) (IL-17(-)) cells arise under Th17-inducing condition and have distinct properties from the Th1 lineage. In fact, these populations displayed characteristics reminiscent to IL-17 single-producing cells, including production of IL-22, CCL20, and induction of antimicrobial gene expression from epithelial cells. Live sorted IL-17(+) and Th17-IFN-gamma(+) cells retained expression of IL-17 or IFN-gamma after culture, respectively, whereas the IL-17(+)/IFN-gamma(+) population was less stable and could also become IL-17 or IFN-gamma single-producing cells. Interestingly, these Th17 subsets became "Th1-like" cells in the presence of IL-12. These results provide novel insights into the relationship and functionality of the Th17 and Th1 subsets and have direct implications for the analysis and relevance of IL-17 and/or IFN-gamma-producing T cells present in patients' peripheral blood and inflamed tissues.
Department of Immunology, Schering-Plough Biopharma, Palo Alto, CA 94304, USA.
Katia
K
Boniface
Wendy M
WM
Blumenschein
Katherine
K
Brovont-Porth
Mandy J
MJ
McGeachy
Beth
B
Basham
Bela
B
Desai
Robert
R
Pierce
Terrill K
TK
McClanahan
Svetlana
S
Sadekova
René
R
de Waal Malefyt
D019070:Cell Lineage / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D018664:Interleukin-12; D007371:Interferon-gamma