Peripheral blood CCR4+CCR6+ and CXCR3 +CCR6+ CD4+ T cells are highly permissive to HIV-1 infection

Annie Gosselin, Patricia Monteiro, Nicolas Chomont, Felipe Diaz-Griffero, Elias A. Said, Simone Fonseca, Vanessa Wacleche, Mohamed El-Far, Mohamed Rachid Boulassel, Jean Pierre Routy, Rafick Pierre Sekaly, Petronela Ancuta

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6 +, CCR4+CCR6-, CXCR3+CCR6 +, and CXCR3+CCR6- T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6 + T cells expressed the HIV coreceptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. CCR4+CCR6- T cells expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. CXCR3+CCR6- T cells expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro. Total CCR6+ T cells compared with CCR6- T cells harbored higher levels of integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of total CCR6 + T cells and those of CCR4+CCR6+ and CXCR3+CCR6+ T cells were diminished in chronically infected HIV-positive subjects, despite viral-suppressive therapy. A high-throughput analysis of cytokine profiles identified CXCR3 +CCR6+ T cells as a major source of TNF-α and CCL20 and demonstrated a decreased TNF-α/IL-10 ratio in CXCR3 +CCR6- T cells. Finally, CCR4+CCR6+ and CXCR3+CCR6+ T cells exhibited gut- and lymph node-homing potential. Thus, we identified CCR4+CCR6+ and CXCR3+CCR6+ T cells as highly permissive to HIV replication, with potential to infiltrate and recruit more CCR6+ T cells into anatomic sites of viral replication. It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6+ T cell subsets.

Original languageEnglish
Pages (from-to)1604-1616
Number of pages13
JournalJournal of Immunology
Volume184
Issue number3
DOIs
Publication statusPublished - Feb 1 2010

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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    Gosselin, A., Monteiro, P., Chomont, N., Diaz-Griffero, F., Said, E. A., Fonseca, S., Wacleche, V., El-Far, M., Boulassel, M. R., Routy, J. P., Sekaly, R. P., & Ancuta, P. (2010). Peripheral blood CCR4+CCR6+ and CXCR3 +CCR6+ CD4+ T cells are highly permissive to HIV-1 infection. Journal of Immunology, 184(3), 1604-1616. https://doi.org/10.4049/jimmunol.0903058