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


CONCLUSIONS
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.
Bento
Cleonice A M
CA
Department of Microbiology and Parasitology, Brazil. cbento@unirio.br
Hygino
Joana
J
Andrade
Regis M
RM
Saramago
Carmen S M
CS
Silva
Renato G
RG
Silva
Agostinho A L
AA
Linhares
Ulisses C
UC
Brindeiro
Rodrigo
R
Tanuri
Amilcar
A
Rosenzwajg
Michelle
M
Klatzmann
David
D
Andrade
Arnaldo F B
AF
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
D019380:Anti-HIV Agents; D016207:Cytokines; D016753:Interleukin-10