Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis

Abstract

Background: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin + T-helper cells (Eomes + Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells. Objectives: Here, investigated immune cell alterations and the pathophysiological role of Eomes + Th cells for disease activity during pregnancy and post-partum in MS. Methods: We enrolled n = 81 pregnant patients with relapsing-remitting MS (RRMS), n = 27 post-partum RRMS and n = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry. Results: While CD3 + CD4 + Th cells were unaffected, CD3 + CD8 + cytotoxic T-cells were elevated post-partum ( p = 0.02) with reduced B-cell frequencies ( p = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( p = 0.02) compared to the third trimester. Frequencies of Eomes + Th and Eomes + Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes + Th cells. However, Eomes + Th cells correlated with lower frequencies of regulatory T-cells during second ( r = −0.42; p < 0.05) and third trimester ( r = −0.37; p < 0.05). Moreover, Eomes + Th cells correlated with frequencies of B-cells during third trimester ( r = 0.54; p = 0.02). Frequencies of Eomes + Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes + Th cells strongly correlated with disability post-partum as assessed using the EDSS ( r = 0.52; p = 0.009). Discussion: Pregnancy in MS is associated with robust immunological alterations. Eomes + Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes + Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.