Ramien C, Yusko EC, Engler JB, Gamradt S, Patas K, Schweingruber N, Willing A, Rosenkranz SC, Diemert A, Harrison A, Vignali M, Sanders C, Robins HS, Tolosa E, Heesen C, Arck PC, Scheffold A, Chan K, Emerson RO, Friese MA, Gold SM.

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.

Cell Rep. 2019 Oct 22;29(4):810-815

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