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

AIDS. 2009 Jan 2;23(1):9-18. doi: 10.1097/QAD.0b013e328317461e.

Abstract

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Interleukin-10 / biosynthesis*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / immunology*
  • Pregnancy Complications, Infectious / virology
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / immunology
  • Virus Replication / drug effects
  • Virus Replication / immunology*
  • Young Adult

Substances

  • Anti-HIV Agents
  • Cytokines
  • Interleukin-10