Late Pregnancy Serum Factors Suppress T Cell Activation in Experimental Autoimmune Encephalomyelitis (EAE) (42.14)

Abstract

Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS thought to be due to an autoimmune response directed against myelin antigens. EAE is a commonly used animal model for MS and shares clinical, histopathologic and immunologic similarities with MS. Profound suppression of the MS and EAE relapse rate is observed during late pregnancy and is followed by a marked increase in disease severity postpartum. We have recently observed that histopathologic progression of EAE is diminished during late pregnancy and is exacerbated post partum. During EAE and late pregnancy, mice were found to have less mononuclear CNS infiltrates, demyelination and axon severing than virgin controls. The purpose of this study was to explore the hypothesis that decreased autoimmune disease during pregnancy is due to immunosuppressive factors present in the serum during late pregnancy. Female SJL/J mice were immunized for EAE using myelin proteolipid protein (PLP) 139–151. T cell proliferation assays were carried out using lymph node (LN) cells stimulated with PLP or anti-CD3 in the presence of 0–3% late pregnancy or virgin mouse sera. LN cells from age and gender matched naïve mice served as controls. Three percent late pregnancy serum suppressed both anti-CD3 and PLP stimulated T cell proliferation as compared to cells cultured with virgin mouse sera. These results demonstrate the broad suppressive potential of late pregnancy serum on T cell activation and may be responsible for amelioration of clinical signs of EAE during late pregnancy. (Supported by NIH grants NS48316 and T32AI055411).