title: The colocalization potential of HIV-specific CD8+ and CD4+ T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid.
abstract: CD4(+) T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8(+) T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8(+) and CD4(+) T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression. The expression of the gut-homing molecules integrin β7, CCR6, and CXCR3 was identified as a "signature" for HIV-specific but not CMV-specific CD4(+) T-cells thus providing a new explanation for their enhanced permissiveness to infection in vivo. HIV-specific CD8(+) T-cells also expressed high levels of integrin β7 and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4(+) versus CD8(+) T-cells. All trans RA (ATRA) upregulated the expression of integrin β7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that HIV-specific CD8(+) T-cells may colocalize in excess with CD4(+) T-cells into the GALT via integrin β7 and CXCR3, but not via CCR6. Considering our previous findings that CCR6(+)CD4(+) T-cells are major cellular targets for HIV-DNA integration in vivo, a limited ability of CD8(+) T-cells to migrate in the vicinity of CCR6(+)CD4(+) T-cells may facilitate HIV replication and dissemination at mucosal sites.
authors.affiliation: Department of Microbiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Vanessa Sue
authors.initials: VS
authors.lastname: Wacleche
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Annie
authors.initials: A
authors.lastname: Gosselin
authors.forename: Patricia
authors.initials: P
authors.lastname: Monteiro
authors.forename: Mathieu
authors.initials: M
authors.lastname: Goupil
authors.forename: Hassen
authors.initials: H
authors.lastname: Kared
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernard
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*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism*; D007641:Keratolytic Agents / Q000494:pharmacology; D054398:Receptors, CCR4 / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C515354:CCR4 protein, human; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; D039641:Integrin beta Chains; D007641:Keratolytic Agents; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; C091368:integrin beta7; D014212:Tretinoin