Phenotypical characterization of human Th17 cells unambiguously identified by surface IL-17A expression.
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 RORgammat 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.
Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, Center for Molecular Neurobiology Hamburg.
Verena
V
Brucklacher-Waldert
Karin
K
Steinbach
Michael
M
Lioznov
Manuela
M
Kolster
Christoph
C
Hölscher
Eva
E
Tolosa
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007375:Interleukin-1 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; C508717:IL17A protein, human; C098680:Il17a protein, mouse; D007375:Interleukin-1; D020381:Interleukin-17; D008565:Membrane Proteins