Significance Reproduction in placental mammals relies on potent control of the mother’s immune system to not attack the developing fetus. As a bystander effect, pregnancy also potently suppresses the activity of the autoimmune disease multiple sclerosis (MS). Here, we report that T cells are able to directly sense progesterone via their glucocorticoid receptor (GR), resulting in an enrichment of regulatory T cells (Tregs). By using an MS animal model, we found that the presence of the GR in T cells is essential to increase Tregs and confer the protective effect of pregnancy, but not for maintaining the pregnancy itself. Better understanding of this tolerogenic pathway might yield more specific therapeutic means to steer the immunological balance in transplantation, cancer, and autoimmunity.