Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

被引:257
作者
Gosselin, Annie [1 ,2 ]
Monteiro, Patricia [1 ,2 ]
Chomont, Nicolas [1 ,2 ]
Diaz-Griffero, Felipe [5 ]
Said, Elias A. [1 ,2 ]
Fonseca, Simone [1 ,2 ]
Wacleche, Vanessa [1 ,2 ]
El-Far, Mohamed [1 ,2 ]
Boulassel, Mohamed-Rachid [4 ]
Routy, Jean-Pierre [3 ,4 ]
Sekaly, Rafick-Pierre [1 ,2 ]
Ancuta, Petronela [1 ,2 ]
机构
[1] Ctr Hosp Univ Montreal, Ctr Rech, St Luc Hosp, Montreal, PQ H2X 1P1, Canada
[2] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada
[3] McGill Univ, Ctr Hlth, Montreal Chest Inst, Immunodeficiency Serv, Montreal, PQ, Canada
[4] McGill Univ, Ctr Hlth, Montreal Chest Inst, Div Hematol, Montreal, PQ, Canada
[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
基金
加拿大健康研究院;
关键词
NECROSIS-FACTOR-ALPHA; GASTROINTESTINAL-TRACT; CXCR4; EXPRESSION; CENTRAL MEMORY; INTERLEUKIN; 22; IN-VIVO; RECEPTOR; REPLICATION; LYMPHOCYTES; DEPLETION;
D O I
10.4049/jimmunol.0903058
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-alpha and CCL20 and demonstrated a decreased TNF-alpha/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. The Journal of Immunology, 2010, 184: 1604-1616.
引用
收藏
页码:1604 / 1616
页数:13
相关论文
共 71 条
[41]   Current concepts in AIDS pathogenesis: Insights from the SIV/macaque model [J].
Lackner, Andrew A. ;
Veazey, Ronald S. .
ANNUAL REVIEW OF MEDICINE, 2007, 58 :461-476
[42]   Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients [J].
Lecureuil, Cedric ;
Combadiere, Behazine ;
Mazoyer, Elodie ;
Bonduelle, Olivia ;
Samri, Assia ;
Autran, Brigitte ;
Debre, Patrice ;
Combadiere, Christophe .
BLOOD, 2007, 109 (09) :3649-3657
[43]   Glycerol monolaurate prevents mucosal SIV transmission [J].
Li, Qingsheng ;
Estes, Jacob D. ;
Schlievert, Patrick M. ;
Duan, Lijie ;
Brosnahan, Amanda J. ;
Southern, Peter J. ;
Reilly, Cavan S. ;
Peterson, Marnie L. ;
Schultz-Darken, Nancy ;
Brunner, Kevin G. ;
Nephew, Karla R. ;
Pambuccian, Stefan ;
Lifson, Jeffrey D. ;
Carlis, John V. ;
Haase, Ashley T. .
NATURE, 2009, 458 (7241) :1034-U113
[44]   Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells [J].
Li, QS ;
Duan, LJ ;
Estes, JD ;
Ma, ZM ;
Rourke, T ;
Wang, YC ;
Reilly, C ;
Carlis, J ;
Miller, CJ ;
Haase, AT .
NATURE, 2005, 434 (7037) :1148-1152
[45]   Gene regulation and DNA damage in the ageing human brain [J].
Lu, T ;
Pan, Y ;
Kao, SY ;
Li, C ;
Kohane, I ;
Chan, J ;
Yankner, BA .
NATURE, 2004, 429 (6994) :883-891
[46]   Chemokines as regulators of T cell differentiation [J].
Luther, SA ;
Cyster, JG .
NATURE IMMUNOLOGY, 2001, 2 (02) :102-107
[47]   Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract [J].
Mehandru, S ;
Poles, MA ;
Tenner-Racz, K ;
Horowitz, A ;
Hurley, A ;
Hogan, C ;
Boden, D ;
Racz, P ;
Markowitz, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (06) :761-770
[48]   CCR5 and CXCR4 expression correlated with X4 and R5 HIV-1 infection yet not sustained replication in Th1 and Th2 cells [J].
Moonis, M ;
Lee, B ;
Bailer, RT ;
Luo, Q ;
Montaner, LJ .
AIDS, 2001, 15 (15) :1941-1949
[49]   Retinoic acid: An educational "vitamin elixir" for gut-seeking T cells [J].
Mora, JR ;
von Andrian, UH .
IMMUNITY, 2004, 21 (04) :458-460
[50]   Identification of a CCR5-expressing T cell subset that is resistant to R5-tropic HIV infection [J].
Oswald-Richter, Kyra ;
Grill, Stacy M. ;
Leelawong, Mindy ;
Tseng, Michelle ;
Kalams, Spyros A. ;
Hulgan, Todd ;
Haas, David W. ;
Unutmaz, Derya .
PLOS PATHOGENS, 2007, 3 (04) :553-565