Human Immunodeficiency Virus (HIV)-Infected CCR6+ Rectal CD4+ T Cells and HIV Persistence On Antiretroviral Therapy

被引:38
作者
Anderson, Jenny L. [1 ,2 ]
Khoury, Gabriela [1 ,2 ]
Fromentin, Remi [3 ,4 ]
Solomon, Ajantha [1 ,2 ]
Chomont, Nicolas [3 ,4 ]
Sinclair, Elizabeth [5 ]
Milush, Jeffrey M. [5 ]
Hartogensis, Wendy [5 ]
Bacchetti, Peter [6 ]
Roche, Michael [1 ,2 ,7 ]
Tumpach, Carolin [1 ,2 ,7 ]
Gartner, Matthew [7 ]
Pitman, Matthew C. [1 ,2 ]
Epling, Christine Lorrie [5 ]
Hoh, Rebecca [5 ]
Hecht, Frederick M. [5 ]
Somsouk, Ma [5 ]
Cameron, Paul U. [1 ,2 ,8 ,9 ]
Deeks, Steven G. [5 ]
Lewin, Sharon R. [1 ,2 ,8 ,9 ]
机构
[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia
[2] Royal Melbourne Hosp, Melbourne, Vic, Australia
[3] Univ Montreal, Ctr Rech CHUM, Montreal, PQ, Canada
[4] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[7] RMIT Univ, Sch Hlth & Biomed Sci, Melbourne, Vic, Australia
[8] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia
[9] Monash Univ, Melbourne, Vic, Australia
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
HIV reservoir; latency; persistence; chemokine receptor; CCR6; CXCR3; chemokines; rectal tissue; lymph node; TH17; CELLS; PERIPHERAL-BLOOD; INFECTED INDIVIDUALS; TRANSCRIPTION FACTOR; IMMUNE ACTIVATION; GUT; REPLICATION; TISSUE; RESERVOIR; COMPARTMENTALIZATION;
D O I
10.1093/infdis/jiz509
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy. Methods. Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4(+) T cells was determined using flow cytometry. Results. Integrated HIV DNA levels in CD4(+) T cells, CCR6(+)CXCR3(+) memory CD4(+) T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6(+) T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6(+) T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines. Conclusions. HIV-infected CCR6(+) CD4(+) T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.
引用
收藏
页码:744 / 755
页数:12
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