Modulation of immune responses during pregnancy in multiple sclerosis
Disease activity of autoimmune disorders such as multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE) is temporarily suppressed by pregnancy. However, whether disease amelioration is due to non-specific immunomodulation or mediated by antigen-specific regulation of disease-causing conventional T cells (Tcon) and immuno-suppressive regulatory T cells (Treg), remains elusive. We systematically analysed changes of the T cell receptor (TCR) repertoire in EAE mice and MS patients and their modulation by pregnancy. In mice, our findings indicate that pregnancy supports the expansion of Treg clonotypes that are equipped to recognize EAE-associated antigens. These Treg are thereby particularly suited to control corresponding encephalitogenic Tcon responses and likely contribute to pregnancy-associated protection in autoimmunity. In a parallel human proof-of-concept approach, we demonstrate that relapse-associated and myelin-specific T cell clones contracted during pregnancy and expanded during a postpartum relapse, providing evidence that profiling the TCR repertoire during pregnancy could serve as a tool to discover and track disease-associated T cell clones in human autoimmunity.