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J Immunol. 2019 Oct 1;203(7):1743-1752. doi: 10.4049/jimmunol.1900611. Epub 2019 Aug 23.

Pregnancy Enables Expansion of Disease-Specific Regulatory T Cells in an Animal Model of Multiple Sclerosis.

Author information

1
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
2
Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, 12203 Berlin, Germany; and.
3
Medizinische Klinik mit Schwerpunkt Psychosomatik, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, 12203 Berlin, Germany.
4
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany; manuel.friese@zmnh.uni-hamburg.de.

Abstract

Disease activity of autoimmune disorders such as multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to nonspecific immunomodulation or mediated by Ag-specific regulation of disease-causing conventional T cells (Tcon) and immunosuppressive regulatory T cells (Tregs) remains elusive. In the current study, we systematically analyzed changes of the TCRβ repertoire driven by EAE and pregnancy using TCR sequencing. We demonstrate that EAE, but not pregnancy, robustly increased TCR repertoire clonality in both peripheral Tcon and Treg. Notably, pregnancy was required for the expansion of Treg harboring the dominant EAE-associated TRBV13-2 chain and increased the frequency of EAE-associated clonotypes within the Treg compartment. Our findings indicate that pregnancy supports the expansion of Treg clonotypes that are equipped to recognize EAE-associated Ags. These Treg are thereby particularly suited to control corresponding encephalitogenic Tcon responses and likely contribute to pregnancy-associated protection in autoimmunity.

PMID:
31444265
DOI:
10.4049/jimmunol.1900611

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