The colocalization potential of HIV-specific CD8 + and CD4 + T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid

Vanessa Sue Wacleche, Nicolas Chomont, Annie Gosselin, Patricia Monteiro, Mathieu Goupil, Hassen Kared, Cécile Tremblay, Nicole Bernard, Mohamed Rachid Boulassel, Jean Pierre Routy, Petronela Ancuta

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14 Citations (Scopus)

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.

Original languageEnglish
Article numbere32964
JournalPLoS One
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 28 2012

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Wacleche, V. S., Chomont, N., Gosselin, A., Monteiro, P., Goupil, M., Kared, H., Tremblay, C., Bernard, N., Boulassel, M. R., Routy, J. P., & Ancuta, P. (2012). The colocalization potential of HIV-specific CD8 + and CD4 + T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid. PLoS One, 7(3), [e32964]. https://doi.org/10.1371/journal.pone.0032964