Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum
Aparajita Saha, Jaclyn Escuduero, Troy Layouni, Barbra Richardson, Sharon Hou, Nelly Mugo, Andrew Mujugira, Connie Celum, Jared M Baeten, Jairam Lingappa, Grace C John-Stewart, Sylvia M LaCourse, Javeed A Shah, Aparajita Saha, Jaclyn Escuduero, Troy Layouni, Barbra Richardson, Sharon Hou, Nelly Mugo, Andrew Mujugira, Connie Celum, Jared M Baeten, Jairam Lingappa, Grace C John-Stewart, Sylvia M LaCourse, Javeed A Shah
Abstract
Background: Pregnancy is a risk factor for progression from latent tuberculosis infection to symptomatic tuberculosis. However, how pregnancy influences T-cell responses to Mycobacterium tuberculosis is unknown.
Methods: We measured M. tuberculosis-specific cytokines, T-cell memory markers, and overall CD4+ and CD8+ T-cell activation by flow cytometry from 49 women (18 with and 31 without HIV) who became pregnant while enrolled in a randomized controlled trial of preexposure prophylaxis for HIV. We analyzed data using COMPASS, an established statistical method for evaluating overall antigen-specific T-cell responses.
Results: Pregnant women with latent tuberculosis infection demonstrated significantly diminished M. tuberculosis-specific CD4+ cytokine responses in the third trimester (COMPASS polyfunctional score [PFS], 0.07) compared before (PFS, 0.15), during (PFS, 0.13 and 0.16), and after pregnancy (PFS, 0.14; P = .0084, Kruskal-Wallis test). Paradoxically, M. tuberculosis-specific CD8+ cytokines and nonspecifically activated T-cells increased during late pregnancy. Nonspecific T-cell activation, a validated biomarker for progression from latent tuberculosis infection to tuberculosis disease, increased in latent tuberculosis infection-positive women postpartum, compared with latent tuberculosis infection-negative women.
Conclusions: Pregnancy-related functional T-cell changes were most pronounced during late pregnancy. Both M. tuberculosis-specific T-cell changes during pregnancy and increases in immune activation postpartum may contribute to increased risk for tuberculosis progression.
Clinical trials registration: NCT0557245.
Trial registration: ClinicalTrials.gov NCT00557245.
Keywords: M. tuberculosis; T cells; T-cell activation; T-cell memory; pregnancy.
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Source: PubMed