Cutting Edge: Human Th17 Cells Are Identified as Bearing CCR2+CCR5− Phenotype1

Recent reports have shown that IL-17-producing CD4+ T cells (Th17 cells) belong to a distinct helper T cell lineage and are critically involved in the pathogenesis of autoimmune diseases and allergies. However, the chemokine receptor profile of Th17 cells remains to be clarified. In this study, we report that human Th17 cells are identified as CCR2+CCR5− memory CD4+ T cells. Analysis of PBMC from healthy donors showed that CCR2+ cells produce much larger amounts of IL-17 than CCR2− cells, indicating the preferential expression of CCR2 on Th17 cells. Notably, CCR2+CCR5− memory CD4+ T cells produced a large amount of IL-17 and little IFN-γ, whereas CCR2+CCR5+ cells reciprocally produced an enormous amount of IFN-γ but little IL-17. Moreover, a higher expression of T-bet was seen in the CCR5+ memory T cells. These results indicate that absence of CCR5 distinguishes human Th17 cells from Th1 cells.

[1]  A. Lovett-racke,et al.  T-bet Regulates the Fate of Th1 and Th17 Lymphocytes in Autoimmunity1 , 2007, The Journal of Immunology.

[2]  J. Flynn,et al.  IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection1 , 2006, The Journal of Immunology.

[3]  D. Littman,et al.  The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells , 2006, Cell.

[4]  H. Weiner,et al.  Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells , 2006, Nature.

[5]  T. Mcclanahan,et al.  IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. , 2006, The Journal of clinical investigation.

[6]  R. D. Hatton,et al.  Transforming growth factor-β induces development of the TH17 lineage , 2006, Nature.

[7]  L. Presta,et al.  Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. , 2006, The Journal of clinical investigation.

[8]  R. J. Hocking,et al.  TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. , 2006, Immunity.

[9]  Ying Wang,et al.  A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 , 2005, Nature Immunology.

[10]  R. D. Hatton,et al.  Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages , 2005, Nature Immunology.

[11]  K. Ley,et al.  Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. , 2005, Immunity.

[12]  M. Goldman,et al.  IL‐23 up‐regulates IL‐10 and induces IL‐17 synthesis by polyclonally activated naive T cells in human , 2005, European journal of immunology.

[13]  T. Mcclanahan,et al.  IL-23 drives a pathogenic T cell population that induces autoimmune inflammation , 2005, The Journal of experimental medicine.

[14]  A. Lindén,et al.  Interleukin-17 family members and inflammation. , 2004, Immunity.

[15]  H. Kidoya,et al.  Involvement of IL-17 in Fas ligand-induced inflammation. , 2004, International immunology.

[16]  R. Kastelein,et al.  Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain , 2003, Nature.

[17]  A. Gurney,et al.  Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17* , 2003, The Journal of Biological Chemistry.

[18]  R. Horuk,et al.  Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells. , 2001, Blood.

[19]  F. Sallusto,et al.  Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. , 2000, Science.

[20]  H. Weiner,et al.  Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the Cc Chemokine Receptor (Ccr2) , 2000, The Journal of experimental medicine.

[21]  W. Kuziel,et al.  Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis , 2000, The Journal of experimental medicine.

[22]  Laurie H Glimcher,et al.  A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment , 2000, Cell.

[23]  K. Sugamura,et al.  Selective expression of a novel surface molecule by human Th2 cells in vivo. , 1999, Journal of immunology.

[24]  C. Mackay,et al.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. , 1998, The Journal of clinical investigation.

[25]  P. Allavena,et al.  Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s , 1998, The Journal of experimental medicine.

[26]  M. Baggiolini,et al.  Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes , 1996, The Journal of experimental medicine.

[27]  W. Fanslow,et al.  Human IL-17: a novel cytokine derived from T cells. , 1995, Journal of immunology.

[28]  R. D. Hatton,et al.  Transforming growth factor-beta induces development of the T(H)17 lineage. , 2006, Nature.

[29]  K. HayGlass,et al.  T cell chemokine receptor expression in human Th1- and Th2-associated diseases. , 2000, Archivum immunologiae et therapiae experimentalis.