Phenotypical Characterization of Human Th17 Cells Unambiguously Identified by Surface IL-17A Expression

被引:56
作者
Brucklacher-Waldert, Verena [2 ,3 ]
Steinbach, Karin [2 ]
Lioznov, Michael [4 ]
Kolster, Manuela [2 ]
Hoelscher, Christoph [5 ,6 ]
Tolosa, Eva [1 ,2 ]
机构
[1] Univ Med Ctr Hamburg Eppendoff, UKE, Dept Immunol, D-20251 Hamburg, Germany
[2] Univ Med Ctr Hamburg Eppendoff, Inst Neuroimmunol & Clin Multiple Sclerosis Res, Ctr Mol Neurobiol Hamburg, D-20251 Hamburg, Germany
[3] Univ Tubingen, Grad Sch Cellular & Mol Neurosci, D-72074 Tubingen, Germany
[4] Univ Med Ctr Hamburg Eppendoff, Interdisciplinary Clin Stem Cell Transplantat, D-20251 Hamburg, Germany
[5] Res Ctr Borstel, Div Infect Immunol, Borstel, Germany
[6] Cluster Excellence Inflammat Interfaces, Borstel, Germany
关键词
GROWTH-FACTOR-BETA; CD4; T-CELLS; ROR-GAMMA-T; NEUTROPHIL RECRUITMENT; TRANSCRIPTION FACTOR; MULTIPLE-SCLEROSIS; CYTOKINE; RECEPTOR; LYMPHOCYTES; CHEMOKINE;
D O I
10.4049/jimmunol.0901000
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 are involved in the defense against bacteria and fungi and play a prominent role in the pathogenesis of autoimmune diseases, but research on human Th17 cells is hindered due to the lack of a surface marker. In this study, we report that a subset of human and mouse CD4(+) T cells as well as human Th17 T cell clones express IL-17A on their surface upon stimulation. Correlation of surface IL-17A expression with intracellular IL-17A production and with ROR gamma t mRNA expression identified surface IL-17A as a specific marker for human and mouse Th17 cells. Phenotype characterization of ex vivo CD4(+) IL-17A(+) cells showed that the chemokines CCR6 and CCR4, costimulatory molecules, as well as CD2 and CD49d were more prominently expressed on these cells than in surface IL-17A(-) cells, supporting the concept of Th17 cells as a potent inflammatory effector subtype. In addition, we generated human Th1, Th1/17 (producing both IFN-gamma and IL-17A), and Th17 T cell clones based on single cell sorting of surface IL-17A(-), IL-17A(int), and IL-17A(high) CD4(+) T cells, respectively, and showed the plasticity of the double producing clones to the cytokine milieu. The identification of surface IL-17A as a marker for Th17 cells should facilitate research on this subset. The Journal of Immunology, 2009, 183: 5494-5501.
引用
收藏
页码:5494 / 5501
页数:8
相关论文
共 44 条
[1]   Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells [J].
Acosta-Rodriguez, Eva V. ;
Rivino, Laura ;
Geginat, Jens ;
Jarrossay, David ;
Gattorno, Marco ;
Lanzavecchia, Antonio ;
Sallusto, Federica ;
Napolitani, Giorgio .
NATURE IMMUNOLOGY, 2007, 8 (06) :639-646
[2]   Phenotypic and functional features of human Th17 cells [J].
Annunziato, Francesco ;
Cosmi, Lorenzo ;
Santarlasci, Veronica ;
Maggi, Laura ;
Liotta, Francesco ;
Mazzinghi, Benedetta ;
Parente, Eliana ;
Fili, Lucia ;
Ferri, Simona ;
Frosali, Francesca ;
Giudici, Francesco ;
Romagnani, Paola ;
Parronchi, Paola ;
Tonelli, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1849-1861
[3]   Specific expression of surface interferon-gamma on interferon-gamma producing T cells from mouse and man [J].
Assenmacher, M ;
Scheffold, A ;
Schmitz, J ;
Checa, JAS ;
Miltenyi, S ;
Radbruch, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (01) :263-267
[4]   LYMPHOTOXIN-BETA, A NOVEL MEMBER OF THE TNF FAMILY THAT FORMS A HETEROMERIC COMPLEX WITH LYMPHOTOXIN ON THE CELL-SURFACE [J].
BROWNING, JL ;
NGAMEK, A ;
LAWTON, P ;
DEMARINIS, J ;
TIZARD, R ;
CHOW, EPC ;
HESSION, C ;
OBRINEGRECO, B ;
FOLEY, SF ;
WARE, CF .
CELL, 1993, 72 (06) :847-856
[5]   Enhanced recognition of protein transmembrane domains with prediction-based structural profiles [J].
Cao, BQ ;
Porollo, A ;
Adamczak, R ;
Jarrell, M ;
Meller, J .
BIOINFORMATICS, 2006, 22 (03) :303-309
[6]   Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor [J].
Cosmi, Lorenzo ;
De Palma, Raffaele ;
Santarlasci, Veronica ;
Maggi, Laura ;
Capone, Manuela ;
Frosali, Francesca ;
Rodolico, Gabriella ;
Querci, Valentina ;
Abbate, Gianfranco ;
Angeli, Roberta ;
Berrino, Liberato ;
Fambrini, Massimiliano ;
Caproni, Marzia ;
Tonelli, Francesco ;
Lazzeri, Elena ;
Parronchi, Paola ;
Liotta, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio ;
Annunziato, Francesco .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (08) :1903-1916
[7]   Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells [J].
Cupedo, Tom ;
Crellin, Natasha K. ;
Papazian, Natalie ;
Rombouts, Elwin J. ;
Weijer, Kees ;
Grogan, Jane L. ;
Fibbe, Willem E. ;
Cornelissen, Jan J. ;
Spits, Hergen .
NATURE IMMUNOLOGY, 2009, 10 (01) :66-74
[8]   IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger [J].
Ferretti, S ;
Bonneau, O ;
Dubois, GR ;
Jones, CE ;
Trifilieff, A .
JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :2106-2112
[9]   T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J].
Fossiez, F ;
Djossou, O ;
Chomarat, P ;
FloresRomo, L ;
AitYahia, S ;
Maat, C ;
Pin, JJ ;
Garrone, P ;
Garcia, E ;
Saeland, S ;
Blanchard, D ;
Gaillard, C ;
DasMahapatra, B ;
Rouvier, E ;
Golstein, P ;
Banchereau, J ;
Lebecque, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (06) :2593-2603
[10]   Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke [J].
Gelderblom, Mathias ;
Leypoldt, Frank ;
Steinbach, Karin ;
Behrens, Doerthe ;
Choe, Chi-Un ;
Siler, Dominic A. ;
Arumugam, Thiruma V. ;
Orthey, Ellen ;
Gerloff, Christian ;
Tolosa, Eva ;
Magnus, Tim .
STROKE, 2009, 40 (05) :1849-1857