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

Patricia Monteiro, Annie Gosselin, Vanessa Sue Wacleche, Mohamed El-Far, Elias A. Said, Hassen Kared, Nathalie Grandvaux, Mohamed Rachid Boulassel, Jean Pierre Routy, Petronela Ancuta

Research output: Contribution to journalArticle

81 Citations (Scopus)

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 α4β7, a newly identified HIV-gp120 binding receptor. In this study, we investigated whether memory T cells coexpressing CCR6 and integrin β7 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 β7 -R6+ and β7 +R6+ compared with β 7 -R6- and β7 +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 α4 and β7 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 β7, is a discriminative marker for memory T cells imprinted with a transcriptional program favorable to HIV replication. Nevertheless, given the ability of integrin β7 to regulate cell migration into the GALT and bind HIV-gp120, CCR6+ T cells coexpressing integrin β7 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.

Original languageEnglish
Pages (from-to)4618-4630
Number of pages13
JournalJournal of Immunology
Volume186
Issue number8
DOIs
Publication statusPublished - Apr 15 2011

ASJC Scopus subject areas

  • Immunology

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