T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis

• Published in: Cell reports (Cambridge) 2019-10, Vol.29 (4), p.810-815.e4
• Main Authors: Ramien, Caren, Yusko, Erik C., Engler, Jan Broder, Gamradt, Stefanie, Patas, Kostas, Schweingruber, Nils, Willing, Anne, Rosenkranz, Sina Cathérine, Diemert, Anke, Harrison, Anja, Vignali, Marissa, Sanders, Catherine, Robins, Harlan S., Tolosa, Eva, Heesen, Christoph, Arck, Petra C., Scheffold, Alexander, Chan, Kenneth, Emerson, Ryan O., Friese, Manuel A., Gold, Stefan M.
• Format: Article
• Language: English
• Subjects: human; immune phenotyping; immune tolerance; immunosequencing; multiple sclerosis; pregnancy; repertoire sequencing; T cell receptor α and β pairing
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.09.025

Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we characterize immunomodulation at the single-clone level by sequencing the T cell repertoire in healthy women and female MS patients over the course of pregnancy. Clonality is significantly reduced from the first to third trimester in MS patients, indicating that the T cell repertoire becomes less dominated by expanded clones. However, only a few T cell clones are substantially modulated during pregnancy in each patient. Moreover, relapse-associated T cell clones identified in an individual patient contract during pregnancy and expand during a postpartum relapse. Our data provide evidence that profiling the T cell repertoire during pregnancy could serve as a tool to discover and track “private” T cell clones associated with disease activity in autoimmunity. [Display omitted] •Pregnancy modulates the T cell repertoire in MS in a clonally specific fashion•“Private” candidate clones associated with disease activity can be identified•Barcoding enables α-β TCR pairing of these clones for further characterization•Most candidate clones do not respond to putative MS autoantigens (e.g., myelin) Ramien et al. interrogate the immune repertoire in multiple sclerosis (MS) during pregnancy. They report a shift in T cell repertoire composition driven by a small number of “private” clones. This specific rather than global immunomodulation may help to explain the protective effect of pregnancy in human autoimmunity.