Mycobacterium tuberculosis-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. Abstract Word Count: 245 Keywords: M. tuberculosis, pregnancy, T cells, T cell memory, T cell activation