Abstract
Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified antigen production is occurring, which suggests a period of compromised HIV-1 control in pregnancy.
Highlights
Following HIV-1 infection, seropositive individuals generate specific immune responses against HIV-1 antigens that contribute to virological control [1,2,3]
Individuals were screened based on their sex, age, and HIV1 status, with 18–45 year old HIV-1 positive women, on or commencing antiretroviral therapy (ART) being eligible for recruitment
White blood cell (WBC) count demonstrated significantly higher results in the PP women on ART, similar to those seen in pregnant HIV-1 negative women, with lymphocyte, eosinophil, and basophil absolute counts showing no change, while monocyte and neutrophil counts were increased from the positive non-pregnant (PnP) group [42]
Summary
Following HIV-1 infection, seropositive individuals generate specific immune responses against HIV-1 antigens that contribute to virological control [1,2,3]. The absolute number of Gag responding CD4 T cells decreases without ART, the maintenance of responsive HIV-1-specific memory T-cell subsets in chronic progressors is associated with slower disease advancement, more gradual T-cell loss and control of background viral replication [9,10,11,12,13,14,15,16] In pregnancy these responses are linked to vertical transmission incidence, with higher Nef responses and interleukin-10 (IL-10) plasma concentrations associated with decreased transmission risk, though few studies have explored these relationships [17, 18]. IFNγ and IL-10 responses to Cytomegalovirus, Epstein-Barr virus and other viruses are reduced in the second trimester, suggesting pregnancy immune response modulation is virus, and potentially antigen, specific [20, 23, 24]
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