Changes in the Vα7.2+ CD161++ MAIT cell compartment in early pregnancy are associated with preterm birth in HIV-positive women

Abstract

Problem: Human immunodeficiency virus (HIV) infection is associated with an increased risk of adverse pregnancy outcomes, including preterm birth (PTB), despite viral suppression with antiretroviral therapy. Mucosal-associated invariant T (MAIT) cells are an immune cell subset involved in antimicrobial immunity at mucosal surfaces. MAIT cells have been found at the maternal-foetal interface, and MAIT cells are typically depleted early in HIV infection. We aimed to investigate changes in MAIT cells in relation to maternal HIV/ART status and PTB.

Method of study: We conducted flow cytometric analysis of peripheral blood samples from 47 HIV-positive (HIV+) and 45 HIV-negative (HIV-) pregnant women enrolled in a prospective pregnancy cohort study in Soweto, South Africa. Frequencies of Vα7.2+ CD161++ MAIT cells and proportions of CD4⁺ , CD8⁺ and double-negative MAIT cells were compared between women with and without HIV infection, and between women with and without PTB or spontaneous preterm labour (Sp-PTL).

Results: Although overall MAIT cell frequencies were the same between HIV+ and HIV- patients, HIV+ patients had a higher proportion of CD8⁺ MAIT cells in the first two trimesters. Women with PTB and Sp-PTL also had a higher proportion of CD8⁺ MAIT cells in the first trimester compared to women without these outcomes. The association between changes in MAIT cell subsets and PTB/Sp-PTL was present in both HIV+ and HIV- women, and an additive effect on MAIT cell subsets was seen in women with both HIV infection and PTB.

Conclusions: Interactions between HIV-related and pregnancy-related changes in MAIT cell subsets and distribution may lead to imbalances in peripheral MAIT cell subsets in early pregnancy. This may contribute to the increased risk of PTB in HIV+ patients by altering the overall functionality of the peripheral MAIT cell compartment.

Keywords: HIV; MAIT cells; antiretroviral therapy; mucosal-associated invariant T cells; preterm birth.