HEAT-SHOCK PROTEINS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS II - ENVIRONMENTAL INFECTION AND EXTRA-NEURAXIAL INFLAMMATION ALTER THE COURSE OF CHRONIC RELAPSING ENCEPHALOMYELITIS

We wished to study how infections might trigger relapses of autoimmune diseases such as multiple sclerosis (MS) and encephalomyelitis (EAE). We hypothesized that immune responses to heat shock proteins (hsp) in duced by an infection could modulate responses to autoantigens. We ind uced extra-neuraxial inflammation in Sn mice housed either in specific -pathogen free (SPF) or conventional facilities. Mice in conventional housing are continuously exposed to large numbers of infectious agents . Spleen cell proliferative responses to human HSP60 and bacterial HSP 65 were measured as were numbers of cells secreting IFN-gamma or IL-5. Proliferative responses to HSP60 were increased in conventionally hou sed mice compared to SPF mice and this was associated with skewing of secreted cytokines toward a Th2 pattern. Skewing toward a Th1 pattern was noted in SPF mice. Acute and relapsing EAE was induced in both gro ups of mice. Acute EAE was, in general, equivalent in all groups. Howe ver, SPF mice had more severe relapses than did conventionally housed animals and these differences were amplified by extra-neuraxial inflam mation. Immunocytochemical analyses of brains from mice with relapsing EAE showed that increased numbers of brain gamma/delta cells were ass ociated with disease remission. Our data suggest that frequent exposur e to infectious agents leads to a relative Th2 skewing of immune respo nses to hsp and that this is associated with milder, less frequent rel apses of EAE. They also support the concept that immune responses to h sp are of potential importance in exacerbating and perpetuating organ- restricted autoimmune diseases. (C) 1998 Elsevier Science B.V. All rig hts reserved.