Human Th17 Cells Comprise Heterogeneous Subsets Including IFN-γ-Producing Cells with Distinct Properties from the Th1 Lineage

被引:151
作者
Boniface, Katia [1 ]
Blumenschein, Wendy M. [2 ]
Brovont-Porth, Katherine [3 ]
McGeachy, Mandy J. [1 ]
Basham, Beth [4 ]
Desai, Bela [3 ]
Pierce, Robert [3 ]
McClanahan, Terrill K. [2 ]
Sadekova, Svetlana [3 ]
Malefyt, Rene de Waal [1 ]
机构
[1] Schering Plough Biopharma, Dept Immunol, Palo Alto, CA 94304 USA
[2] Schering Plough Biopharma, Dept Expt Pathol & Pharmacol, Palo Alto, CA 94304 USA
[3] Schering Plough Biopharma, Dept Anat Pathol, Palo Alto, CA 94304 USA
[4] Schering Plough Biopharma, Dept Mol Design & Informat, Palo Alto, CA 94304 USA
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROTEOGLYCAN-INDUCED ARTHRITIS; HELPER; 17; CELLS; T-CELL; MULTIPLE-SCLEROSIS; INTESTINAL INFLAMMATION; TRANSCRIPTION FACTOR; INTERLEUKIN; 22; DIFFERENTIATION; IL-17;
D O I
10.4049/jimmunol.1000366
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. The Journal of Immunology, 2010, 185: 679-687.
引用
收藏
页码:679 / 687
页数:9
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