Astrocytes induce hyporesponses of myelin basic protein-reactive T and B cell function

Abstract

We have isolated infiltrating mononuclear cells (inMNC) and lymph node MNC (lnMNC) from Lewis rats with actively induced experimental allergic encephalomyelitis (EAE), and compared their responses to myelin basic protein (MBP). MBP-induced proliferation and MBP-specific IgG secreting cells were lower in inMNC compared to lnMNC, while MBP-reactive IFN- γ secreting cells in inMNC were higher. Using an in vitro culture system, we observed that astrocytes derived from newborn Lewis rats not only suppressed T cell proliferation and IFN- γ production but also reduced MBP-specific IgG production by B cells. Astrocyte-derived soluble factor (s), rather than direct cell-to-cell interactions, seems to be responsible for the inhibitory effect. Supernatants from IFN- γ-stimulated astrocytes exhibited stronger suppressive effects than supernatants from unstimulated astrocytes, whereas supernatants from microglia did not cause downregulation of T and B cell functions. These results indicate that astrocytes are major effector cells in inhibiting functions of MBP-reactive T and B cells. Astrocytes down-regulated expression of ICAM-1 and MHC class II in lnMNC, but did not induce apoptosis of lnMNC. The results in the present study do not exclude the possibility that astrocytes induce T cell apoptosis in a cognate fashion. Taken together, the inhibitory properties of astrocytes may contribute to the confinement of inflammatory lesions in multiple sclerosis and EAE. Our report compares immunoreactivities of inMNC and lnMNC in EAE and elucidates the role of astrocytes in the inactivation of MBP-reactive T and B cells.