T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis

Abstract

Identifying Tcell 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 Tcell 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 Tcell repertoire becomes less dominated by expanded clones. However, only a few Tcell clones are substantially modulated during pregnancy in each patient. Moreover, relapse-associated Tcell clones identified in an individual patient contract during pregnancy and expand during a postpartum relapse. Our data provide evidence that profiling the Tcell repertoire during pregnancy could serve as a tool to discover and track "private" Tcell clones associated with disease activity in autoimmunity.