TY - JOUR
T1 - Peripheral blood CCR4+CCR6+ and CXCR3 +CCR6+ CD4+ T cells are highly permissive to HIV-1 infection
AU - Gosselin, Annie
AU - Monteiro, Patricia
AU - Chomont, Nicolas
AU - Diaz-Griffero, Felipe
AU - Said, Elias A.
AU - Fonseca, Simone
AU - Wacleche, Vanessa
AU - El-Far, Mohamed
AU - Boulassel, Mohamed Rachid
AU - Routy, Jean Pierre
AU - Sekaly, Rafick Pierre
AU - Ancuta, Petronela
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.0903058
DO - 10.4049/jimmunol.0903058
M3 - Article
C2 - 20042588
AN - SCOPUS:77949320175
SN - 0022-1767
VL - 184
SP - 1604
EP - 1616
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -