Pregnancy favors circulating IL-21-secreting TFH -like cell recovery in ARV-treated HIV-1-infected women

Am J Reprod Immunol. 2020 Feb;83(2):e13204. doi: 10.1111/aji.13204. Epub 2019 Nov 17.

Abstract

Problem: Pregnancy appears to favor maternal antibody production. In contrast, by damaging follicular helper T cells (TFH ), HIV-1 infection compromises protective humoural immune response. Therefore, we aimed to investigate the frequency of different TFH -like cells in HIV-infected pregnant women (PW) before and after antiretroviral (ARV) therapy.

Method of study: Peripheral blood mononuclear cells, CD4+ T and B cells, were obtained from asymptomatic HIV-1-infected non-PW and PW just before and after ARV therapy. In some experiments, healthy HIV-1-negative PW were also tested. The frequency of different TFH -like cell subsets was determined by flow cytometry. The plasma titers of IgG anti-tetanus toxoid (TT), anti-HBsAg, and anti-gp41 were determined by ELISA. The in vitro production of total IgG, IL-21, and hormones (estrogen and progesterone) was quantified also by ELISA.

Results: Our results demonstrate that antiretroviral (ARV) therapy was more efficient in elevating the percentage of circulating IL-21-secreting TFH cells in HIV-1-infected pregnant women (PW) than in non-pregnant patients (nPW). Moreover, in co-culture systems, CD4+ T cells from ART-treated PW were more efficient in assisting B cells to produce IgG production. The in vivo anti-HBsAg IgG titers after ARV therapy were also significantly higher in PW, and their levels were directly associated with both IL-21+ TFH frequency and plasma concentration of estrogen.

Conclusion: In summary, our results suggest that pregnancy favors the recovery of TFH -like cells after ARV therapy in HIV-1-infected women, which could help these mothers to protect their newborns from infectious diseases by transferring IgG across the placenta.

Keywords: HIV-1; IgG; TFH cells; antiretroviral therapy; estrogen.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Bacterial / blood
  • Antibody Formation / drug effects
  • B-Lymphocytes / drug effects
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Coculture Techniques
  • Estrogens / blood
  • Female
  • HIV Antibodies / blood
  • HIV Envelope Protein gp41 / immunology
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1* / immunology
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / immunology
  • Humans
  • Immunoglobulin G / blood
  • Interleukins / metabolism*
  • Pregnancy
  • Pregnancy Complications, Infectious / blood
  • Pregnancy Complications, Infectious / immunology*
  • Progesterone / blood
  • T Follicular Helper Cells / metabolism*
  • Tetanus Toxoid / immunology
  • Young Adult

Substances

  • Anti-HIV Agents
  • Antibodies, Bacterial
  • Estrogens
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Immunoglobulin G
  • Interleukins
  • Tetanus Toxoid
  • gp41 protein, Human immunodeficiency virus 1
  • Progesterone
  • interleukin-21