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
[1]   Regulatory T cells mediate maternal tolerance to the fetus [J].
Aluvihare, VR ;
Kallikourdis, M ;
Betz, AG .
NATURE IMMUNOLOGY, 2004, 5 (03) :266-271
[2]  
[Anonymous], 1987, MMWR-MORBID MORTAL W
[3]   Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells [J].
Bahbouhi, B ;
Landay, A ;
Al-Harthi, L .
BLOOD, 2004, 103 (12) :4581-4587
[4]   CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity [J].
Belkaid, Y ;
Piccirillo, CA ;
Mendez, S ;
Shevach, EM ;
Sacks, DL .
NATURE, 2002, 420 (6915) :502-507
[5]   Microbial translocation is a cause of systemic immune activation in chronic HIV infection [J].
Brenchley, Jason M. ;
Price, David A. ;
Schacker, Timothy W. ;
Asher, Tedi E. ;
Silvestri, Guido ;
Rao, Srinivas ;
Kazzaz, Zachary ;
Bornstein, Ethan ;
Lambotte, Olivier ;
Altmann, Daniel ;
Blazar, Bruce R. ;
Rodriguez, Benigno ;
Teixeira-Johnson, Leia ;
Landay, Alan ;
Martin, Jeffrey N. ;
Hecht, Frederick M. ;
Picker, Louis J. ;
Lederman, Michael M. ;
Deeks, Steven G. ;
Douek, Daniel C. .
NATURE MEDICINE, 2006, 12 (12) :1365-1371
[6]  
CABERA R, 2004, HEPATOLOGY, V40, P1062
[7]   The inhibition of HIV replication in monocytes by interleukin 10 is linked to inhibition of cell differentiation [J].
Chang, J ;
Naif, HM ;
Li, S ;
Jozwiak, R ;
HoShon, M ;
Cunningham, AL .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1996, 12 (13) :1227-1235
[8]   Post-partum acute exacerbation of chronic hepatitis in a hepatitis C-carrier mother [J].
Chen, JD ;
Chung, JL ;
Kao, JH ;
Chen, DS .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2001, 16 (06) :705-708
[9]   ROLE OF INTERLEUKIN-10 IN T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC INDIVIDUALS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS [J].
CLERICI, M ;
WYNN, TA ;
BERZOFSKY, JA ;
BLATT, SP ;
HENDRIX, CW ;
SHER, A ;
COFFMAN, RL ;
SHEARER, GM .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :768-775
[10]   Maternal infection and risk of preeclampsia: Systematic review and metaanalysis [J].
Conde-Agudelo, Agustin ;
Villar, Jose ;
Lindheimer, Marshall .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2008, 198 (01) :7-22