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

A Gosselin, P Monteiro, N Chomont… - The Journal of …, 2010 - journals.aai.org
A Gosselin, P Monteiro, N Chomont, F Diaz-Griffero, EA Said, S Fonseca, V Wacleche…
The Journal of Immunology, 2010journals.aai.org
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 …
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.
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