title: Dynamics of regulatory T-cells during pregnancy: effect of HIV infection and correlations with other immune parameters.
abstract: OBJECTIVE
  Regulatory T cells (Treg) increase in the context of HIV infection and pregnancy. We studied Treg subpopulations in HIV-infected and uninfected women during pregnancy and their relationship with inflammation, activation and cell-mediated immunity (CMI).
  
  
  METHODS
  Blood obtained from 20 HIV-infected and 18 uninfected women during early and late gestation was used to measure Treg and activated T cells (Tact) by flow cytometry; plasma cytokines and inflammatory markers by ELISA and chemoluminescence; and CMI against varicella-zoster virus (VZV) by lymphocyte proliferation.
  
  
  CONCLUSIONS
  Compared with uninfected women, HIV-infected participants had higher frequencies of Treg subpopulations in early pregnancy, including CD4+CD25+FoxP3+%, CD8+CD25+FoxP3+%, CD4+TGFβ+% and CD4+IL10+%. In contrast, Treg frequencies were lower during late pregnancy in HIV-infected compared with uninfected women, including CD8+TGFβ+%, CD4+CTLA4+% and CD8+CTLA4+%. VZV-CMI, which was lower in HIV-infected compared with uninfected pregnant women, was inversely correlated with CD4+FoxP3+%, CD8+FoxP3+% and CD8+TGFβ+% in HIV-infected, but not in uninfected pregnant women. β₂-microglobulin, neopterin, IL1, IL4, IL8, IL10, IFNγ and TNFα plasma concentrations as well as Tact were higher in HIV-infected compared with uninfected women throughout pregnancy. In HIV-infected, but not in uninfected women, inflammatory, Th1, Th2 and regulatory cytokines increased with higher Treg%, suggesting that inflammation and regulation have a common pathophysiologic origin in the context of HIV infection. In HIV-infected and more commonly in uninfected pregnant women, higher Treg% correlated with lower Tact%. We conclude that Treg have different dynamics during pregnancy in HIV-infected and uninfected women. Higher levels of inflammatory cytokines and lower Treg% during late pregnancy in HIV-infected women may contribute to their increased incidence of maternal-fetal morbidity.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Richardson
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D049590:Postpartum Period / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators