SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell‐mediated disease of the central nervous system. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report that SAP‐transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in complete Freund's adjuvant, SAP‐transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However, in SAP‐Knockout mice, the severity of EAE is enhanced. Adoptive transfer of Ag‐restimulated T cells from wild type to SAP‐transgenic mice, or transfer of SAP‐transgenic Ag‐restimulated T cells to control mice, induced milder EAE. T cells from MOG‐primed SAP‐transgenic mice showed weak proliferative responses. Furthermore, in SAP‐transgenic mice, there is little infiltration of CD45‐positive cells in the spinal cord. In vitro, SAP suppressed the secretion of interleukin‐2 stimulated by P‐selectin and blocked P‐selectin binding to T cells. Moreover, SAP could change the affinity between α4‐integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P‐selectin.