MALE SJL MICE DO NOT RELAPSE AFTER INDUCTION OF EAE WITH PLP-139-151

SJL mice immunized with proteolipid protein (PLP) develop relapsing ex perimental autoimmune encephalomyelitis (R-EAE). R-EAE is a CD4(+), Th 1 cell-mediated demyelinating disease of the central nervous system (C NS) that is used as a model for the human disease multiple sclerosis ( MS). Previous studies showed that young (<8 weeks) male SJL mice were resistant to active induction of EAE with CNS homogenate, while female mice were susceptible, We have recently observed that young male SJL mice immunized with a major encephalitogenic peptide of myelin, PLP 13 9-151, developed initial clinical and histological symptoms of EAE wit h a severity similar to age-matched females; however, unlike females, male mice did not relapse, Significant T cell proliferation to PLP 139 -151, but not to other PLP and myelin basic protein (MBP) epitopes, wa s observed in both males and females during the initial episode, recov ery, and first relapse of clinical disease, Reverse transcriptase-poly merase chain reaction (RT-PCR) analysis of lymphokine mRNA revealed di fferences in IFN-gamma and IL-4 synthesis consistent with the hypothes is that Th2 T cells develop in young male SJL mice that regulate the r elapsing phase of the disease, These data suggest that immunization of young male SJL mice with PLP 139-151 overrides a defect in antigen pr esentation responsible for the previously observed resistance to EAE, and that natural processing and presentation of neuroantigens during t he course of acute EAE induces Th2 cells that prevent the relapse of d isease, (C) 1996 Wiley-Liss, Inc.