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Pregnancy gestation impacts on HIV-1-specific granzyme B response and central memory CD4 T cells

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Title: Pregnancy gestation impacts on HIV-1-specific granzyme B response and central memory CD4 T cells
Authors: Cocker, A
Shah, N
Raj, I
Dermont, S
Khan, W
Mandalia, S
Imami, N
Johnson, M
Item Type: Journal Article
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.
Issue Date: 11-Feb-2020
Date of Acceptance: 21-Jan-2020
URI: http://hdl.handle.net/10044/1/77290
DOI: 10.3389/fimmu.2020.00153
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 11
Copyright Statement: © 2020 Cocker, Shah, Raj, Dermont, Khan, Mandalia, Imami and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Imperial College Trust
St Stephen's Aids Trust
Westminster Medical School Research Trust
Westminster Medical School Research Trust
Funder's Grant Number: Mark Johnson's IC Trust Acct
PHD 001 03/15-16
JRC PHD 001 03/15-16
Keywords: Gag and Nef
T-cell responses
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 153
Appears in Collections:Department of Infectious Diseases