Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7

J Immunol. 2011 Apr 15;186(8):4618-30. doi: 10.4049/jimmunol.1004151. Epub 2011 Mar 11.


HIV type 1 infection is associated with a rapid depletion of Th17 cells from the GALT. The chemokine receptor CCR6 is a marker for Th17 lineage polarization and HIV permissiveness in memory CD4(+) T cells. CCR6(+) T cells have the potential to migrate into the GALT via the gut-homing integrin α(4)β(7), a newly identified HIV-gp120 binding receptor. In this study, we investigated whether memory T cells coexpressing CCR6 and integrin β(7) are selective HIV targets and whether retinoic acid (RA)-induced imprinting for gut-homing selectively increases CCR6(+) T cell permissiveness to infection. We demonstrated that β(7)(-)R6(+) and β(7)(+)R6(+) compared with β(7)(-)R6(-) and β(7)(+)R6(-) T cells were highly permissive to HIV, produced Th17 cytokines, and their frequency was decreased in the peripheral blood of HIV-infected subjects. RA upregulated integrin α(4) and β(7) coexpression in both CCR6(+) and CCR6(-) T cells, but increased HIV permissiveness selectively in CCR6(+) T cells via entry (CCR5 upregulation) and postentry mechanisms. In conclusion, these results demonstrate that CCR6, but not the integrin β(7), is a discriminative marker for memory T cells imprinted with a transcriptional program favorable to HIV replication. Nevertheless, given the ability of integrin β(7) to regulate cell migration into the GALT and bind HIV-gp120, CCR6(+) T cells coexpressing integrin β(7) and CCR5 might have an extraordinary ability to disseminate HIV from the portal sites of entry. Understanding the molecular mechanisms of memory CCR6(+) T cell differentiation is critical for the design of new therapeutic strategies that should interfere with viral permissiveness but not Th17 lineage commitment and gut-homing potential in CCR6(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • DNA, Viral / genetics
  • Flow Cytometry
  • HEK293 Cells
  • HIV Infections / blood
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunologic Memory / immunology
  • Integrin alpha4 / immunology
  • Integrin alpha4 / metabolism
  • Integrin beta Chains / immunology*
  • Integrin beta Chains / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Polymerase Chain Reaction
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism
  • Receptors, CCR6 / immunology*
  • Receptors, CCR6 / metabolism
  • Tretinoin / pharmacology
  • Virus Replication / drug effects
  • Virus Replication / genetics


  • CCR6 protein, human
  • DNA, Viral
  • Integrin beta Chains
  • Interleukin-17
  • Receptors, CCR5
  • Receptors, CCR6
  • integrin beta7
  • Integrin alpha4
  • Tretinoin