IL-10-secreting T cells from HIV-infected pregnant women downregulate HIV-1 replication: effect enhanced by antiretroviral treatment

被引:25
作者
Bento, Cleonice A. M. [1 ]
Hygino, Joana [1 ]
Andrade, Regis M. [1 ]
Saramago, Carmen S. M. [1 ]
Silva, Renato G. [1 ]
Silva, Agostinho A. L. [1 ]
Linhares, Ulisses C. [2 ]
Brindeiro, Rodrigo [3 ]
Tanuri, Amilcar [3 ]
Rosenzwajg, Michelle [4 ]
Klatzmann, David [4 ]
Andrade, Arnaldo F. B. [5 ]
机构
[1] Univ Fed Rio de Janeiro, Dept Microbiol & Parasitol, BR-20261040 Rio De Janeiro, Brazil
[2] Univ Fed Rio de Janeiro, Dept Anat, BR-20261040 Rio De Janeiro, Brazil
[3] Univ Fed Rio de Janeiro, Dept Genet, BR-20261040 Rio De Janeiro, Brazil
[4] Univ Paris 06, CNRS, UPCM UMR 7087, Lab Biol & Therapeut Pathol Immunitaires, Paris, France
[5] Univ Estado Rio De Janeiro, Dept Microbiol, Rio De Janeiro, Brazil
关键词
antiretroviral therapy; cytokines; HIV; interleukin-10; pregnancy; tumor necrosis factor-alpha; HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; IMMUNE ACTIVATION; CHRONIC HEPATITIS; HUMAN MACROPHAGES; VIRAL-LOAD; IN-VITRO; INTERLEUKIN-10; CD4(+); TYPE-1;
D O I
10.1097/QAD.0b013e328317461e
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: This study aimed to evaluate the impact of pregnancy-related immune events on the HIV-1 replication and to analyze their relationship with the risk of vertical transmission. Methods: The peripheral blood from HIV-1-infected pregnant women who controlled (G1) or not controlled (G2) their plasma viral load was drawn, and the plasma and the T cells were obtained. The T-cell cultures were activated in vitro with anti-CD3 and anti-CD28, and the proliferation and cytokine production profile were evaluated after 3 days of incubation. The in-vitro HIV-1 replication was measured in culture supernatants in the seventh day following stimulation. The cytokines were also analyzed in the plasma. Results: Our results demonstrated a lower T-cell proliferation and a lower interleukin-1 beta, tumor necrosis factor-alpha and interferon-gamma production in polyclonally activated T-cell cultures from G1 patients, when compared with G2. Furthermore, high levels of interleukin-10 were produced both systemically and by activated T-cell cultures from G1 patients. Interestingly, the neutralization of endogenous interleukin-10 bby anti-interleukin-10 monoclonal antibody elevated both the inflammatory cytokines' release and the HIV-1 replication in the polyclonally activated T-cell cultures from G1 patients. Additionally, the maternal antiretroviral treatment significantly enhanced the systemic interleukin-10 production. Finally, the higher systemic interleukin-10 levels were inversely correlated with vertical virus transmission risk. Conclusion: These results indicate that a high tendency of pregnant women to produce interleukin-10 can help them control the HIV-1 replication, and this can reduce the risk of vertical transmission. Furthermore, our data suggest a role for maternal antiretroviral treatment in enhancing this phenomenon. (C) 2009 Wolters Kluwer Health vertical bar Lippincolt Williams & Wilkins
引用
收藏
页码:9 / 18
页数:10
相关论文
共 49 条
[21]  
KINTER AL, 1995, J IMMUNOL, V154, P2448
[22]   INTERFERENCE OF INTERLEUKIN-10 WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN PRIMARY MONOCYTE-DERIVED MACROPHAGES [J].
KOOTSTRA, NA ;
VANTWOUT, AB ;
HUISMAN, HG ;
MIEDEMA, F ;
SCHUITEMAKER, H .
JOURNAL OF VIROLOGY, 1994, 68 (11) :6967-6975
[23]   Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis [J].
Kourtis, Athena P. ;
Schmid, Christopher H. ;
Jamieson, Denise J. ;
Lau, Joseph .
AIDS, 2007, 21 (05) :607-615
[24]   'Modeling' relationships among HIV-1 replication, immune activation and CD4+T-cell losses using adjusted correlative analyses [J].
Lederman, MM ;
Kalish, LA ;
Asmuth, D ;
Fiebig, E ;
Mileno, M ;
Busch, MP .
AIDS, 2000, 14 (08) :951-958
[25]   Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease [J].
Li, TS ;
Tubiana, R ;
Katlama, C ;
Calvez, V ;
Ait Mohand, H ;
Autran, B .
LANCET, 1998, 351 (9117) :1682-1686
[26]   Antiretroviral therapy - Optimal Sequencing of therapy to avoid resistance [J].
Martinez-Cajas, Jorge L. ;
Wainberg, Mark A. .
DRUGS, 2008, 68 (01) :43-72
[27]   IL-10 INHIBITS HIV-1 REPLICATION AND IS INDUCED BY TAT [J].
MASOOD, R ;
LUNARDIISKANDAR, Y ;
MOUDGIL, T ;
ZHANG, Y ;
LAW, RE ;
HUANG, CL ;
PURI, RK ;
LEVINE, AM ;
GILL, PS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 202 (01) :374-383
[28]   Increased HIV-1 mucosal replication is associated with generalized mucosal cytokine activation [J].
McGowan, I ;
Elliott, J ;
Fuerst, M ;
Taing, P ;
Boscardin, J ;
Poles, M ;
Anton, P .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2004, 37 (02) :1228-1236
[29]   INTERLEUKIN-10 INHIBITS INITIAL REVERSE TRANSCRIPTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND MEDIATES A VIROSTATIC LATENT STATE IN PRIMARY BLOOD-DERIVED HUMAN MACROPHAGES IN-VITRO [J].
MONTANER, LJ ;
GRIFFIN, P ;
GORDON, S .
JOURNAL OF GENERAL VIROLOGY, 1994, 75 :3393-3400
[30]   Cytokines and pregnancy in rheumatic disease [J].
Ostensen, Monika ;
Foerger, Frauke ;
Villiger, Peter M. .
BASIC AND CLINICAL ASPECTS OF NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC DISEASES, 2006, 1069 :353-363