T cell repertoire dynamics during pregnancy in multiple sclerosis

Abstract

Identifying T cell clones associated with autoimmunity has remained challenging. Intriguingly, many human 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 in individual patients. Here, we characterized immunomodulation at the single clone level by sequencing the T cell receptor (TCR) repertoire in healthy women and female MS patients longitudinally over the course of pregnancy. Clonality was significantly reduced from the first to the third trimester of pregnancy in MS patients, indicating that the TCR repertoire during MS pregnancy becomes less dominated by expanded clones. Only few T cell clones were substantially modulated during pregnancy. In a proof-of-concept approach, we demonstrate that relapse-associated T cell clones identified in an individual patient contracted during pregnancy and expanded during a postpartum relapse. Our data provide evidence that profiling the TCR repertoire during pregnancy could serve as a tool to discover and track “private” T cell clones that are associated with disease activity in individual patients.