T Cell Repertoire Dynamics during Pregnancy in Multiple Sclerosis

Cell Rep. 2019 Oct 22;29(4):810-815.e4. 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Humans
  • Immunophenotyping
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / immunology
  • Pregnancy
  • Pregnancy Complications / blood*
  • Pregnancy Complications / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology*


  • Biomarkers
  • Receptors, Antigen, T-Cell