title: Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals.
abstract: Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.
authors.affiliation: INSERM, UMR1043, Toulouse, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Mavigner
authors.forename: Michelle
authors.initials: M
authors.lastname: Cazabat
authors.forename: Martine
authors.initials: M
authors.lastname: Dubois
authors.forename: Fatima-Ezzahra
authors.initials: FE
authors.lastname: L'Faqihi
authors.forename: Mary
authors.initials: M
authors.lastname: Requena
authors.forename: Christophe
authors.initials: C
authors.lastname: Pasquier
authors.forename: Pascale
authors.initials: P
authors.lastname: Klopp
authors.forename: Jacques
authors.initials: J
authors.lastname: Amar
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Karl
authors.initials: K
authors.lastname: Barange
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vinel
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.forename: Patrice
authors.initials: P
authors.lastname: Massip
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.forename: Pierre
authors.initials: P
authors.lastname: Delobel
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D039641:Integrin beta Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054388:Receptors, CCR / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D039641:Integrin beta Chains; D012333:RNA, Messenger; D054388:Receptors, CCR; C091368:integrin beta7