title: Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Montreal, Montreal, H3C 3J7 Quebec, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Monteiro
authors.forename: Annie
authors.initials: A
authors.lastname: Gosselin
authors.forename: Vanessa Sue
authors.initials: VS
authors.lastname: Wacleche
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Far
authors.forename: Elias A
authors.initials: EA
authors.lastname: Said
authors.forename: Hassen
authors.initials: H
authors.lastname: Kared
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grandvaux
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D005434:Flow Cytometry; D057809:HEK293 Cells; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D039441:Integrin alpha4 / Q000276:immunology / Q000378:metabolism; D039641:Integrin beta Chains / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: C106311:CCR6 protein, human; D004279:DNA, Viral; D039641:Integrin beta Chains; D020381:Interleukin-17; D019713:Receptors, CCR5; D054399:Receptors, CCR6; C091368:integrin beta7; D039441:Integrin alpha4; D014212:Tretinoin