Evidence that Pregnancy Specific Glycoproteins Regulate T-Cell Function and Inflammatory Autoimmune Disease During Pregnancy

The capacity of the pregnancy state to regulate T-cell function is well documented. A consequence of this regulation is that many T-cell mediated autoimmune disorders, including multiple sclerosis (MS) are suppressed during pregnancy. The suppression of MS during pregnancy is more potent than the currently available treatments for this disease. Thus, the study of immunoregulatory factors of pregnancy could potentially result in the discovery of novel MS treatments. The regulation of T-cell function during pregnancy is likely the result of significant hormonal changes and may well involve immunoregulatory proteins derived from the placenta. Pregnancy specific glycoproteins (PSGs) are the most abundant placentally derived glycoproteins in the maternal serum. The levels of PSGs are highest during the third trimester of pregnancy, a time marked by the most profound suppression of MS disease attacks. Recent studies by our laboratories, and others, suggest that PSGs regulate T-cell function. We propose this regulation occurs by two distinct, but complementary mechanisms. PSGs may regulate T-cell function by (1) directly signaling tetraspanins present on the cell surface and by (2) regulating T-cell function indirectly through signaling of tetraspanins expressed by macrophages and dendritic cells. In this report, we will review evidence implicating PSGs as important immunoregulatory proteins and discuss our recent findings regarding the mechanisms by which PSGs regulate T-cell function.