<i>Mycobacterium tuberculosis</i> -specific T cell responses are impaired during late pregnancy with elevated biomarkers of tuberculosis risk postpartum

Abstract Rationale Pregnancy is a risk factor for progression from latent tuberculosis infection (LTBI) to symptomatic tuberculosis (TB). However, how dynamic immunologic changes in pregnancy influence immune responses to M. tuberculosis (Mtb) is unknown. Objectives We performed a detailed characterization of Mtb-specific T cell responses of women at high risk for Mtb infection, leveraging a biorepository of longitudinally samples collected before, during, and after pregnancy in high HIV/TB burden settings. Methods We used specimens collected from women who became pregnant while enrolled in a randomized controlled trial of pre-exposure prophylaxis for HIV prevention. We measured Mtb-specific cytokines, CCR7 and CD45RA memory markers, and overall CD4+ and CD8+ T cell activation from 49 women using COMPASS, a Bayesian statistical method for evaluating overall antigen-specific T cell responses measured by flow cytometry. Measurements and Main Results 22 LTBI+ women, defined by flow cytometry, demonstrated significantly diminished Mtb-specific CD4+ cytokine responses in the third trimester (COMPASS score (PFS) 0.07) compared before (PFS 0.15), during (PFS 0.13 and 0.16), and after pregnancy (PFS 0.14; p = 0.0084, Kruskal-Wallis test). Paradoxically, Mtb-specific CD8+ cytokine responses and nonspecifically activated CD38+HLA-DR+CD4+ T cells increased during late pregnancy. Nonspecific T cell activation, a previously validated biomarker for progression from LTBI to TB disease, was increased in LTBI+ women postpartum, compared with LTBI-women. Conclusions Pregnancy-related functional T cell changes were most pronounced during late pregnancy. Mtb-specific T cell changes during pregnancy and postpartum, increases in immune activation may contribute to increased risk for TB progression in the postpartum period.