Cell Reports (Oct 2019)

T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis

  • Caren Ramien,
  • Erik C. Yusko,
  • Jan Broder Engler,
  • Stefanie Gamradt,
  • Kostas Patas,
  • Nils Schweingruber,
  • Anne Willing,
  • Sina Cathérine Rosenkranz,
  • Anke Diemert,
  • Anja Harrison,
  • Marissa Vignali,
  • Catherine Sanders,
  • Harlan S. Robins,
  • Eva Tolosa,
  • Christoph Heesen,
  • Petra C. Arck,
  • Alexander Scheffold,
  • Kenneth Chan,
  • Ryan O. Emerson,
  • Manuel A. Friese,
  • Stefan M. Gold

Journal volume & issue
Vol. 29, no. 4
pp. 810 – 815.e4

Abstract

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Summary: 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. : 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. Keywords: multiple sclerosis, pregnancy, T cell receptor α and β pairing, immunosequencing, repertoire sequencing, immune phenotyping, immune tolerance, human