Relapses Of Encephalomyelitis Research Articles

Lipopolysaccharide Injection Induces Relapses of Experimental Autoimmune Encephalomyelitis in Nontransgenic Mice via Bystander Activation of Autoreactive CD4+ Cells

Infections sometimes associate with exacerbations of autoimmune diseases through pathways that are poorly understood. Ag-specific mechanisms such as cross-reactivity between a microbial Ag and a self-Ag have received no direct support. In this study, we show that injection of LPS induces experimental autoimmune encephalomyelitis in TCR-transgenic mice and relapse of encephalomyelitis in normal mice. This form of treatment induces proliferation and cytokine production in a fraction of effector/memory Th lymphocytes in vitro via physical contact of Th cells with CD4(-) LPS-responsive cells. TCR-mediated signals are not necessary; rather what is required is ligation of costimulatory receptors on Th cells by costimulatory molecules on the CD4(-) cells. This form of bystander activation provides an Ag-independent link between infection and autoimmunity that might fit the clinical and epidemiological data on the connection between infection and autoimmunity better than the Ag-specific models.

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) induced by an infection could modulate responses to autoantigens. We induced extra-neuraxial inflammation in SJL 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 HSP65 were measured as were numbers of cells secreting IFN-γ or IL-5. Proliferative responses to HSP60 were increased in conventionally housed 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 groups of mice. Acute EAE was, in general, equivalent in all groups. However, SPF mice had more severe relapses than did conventionally housed animals and these differences were amplified by extra-neuraxial inflammation. Immunocytochemical analyses of brains from mice with relapsing EAE showed that increased numbers of brain γ/δ cells were associated with disease remission. Our data suggest that frequent exposure to infectious agents leads to a relative Th2 skewing of immune responses to hsp and that this is associated with milder, less frequent relapses of EAE. They also support the concept that immune responses to hsp are of potential importance in exacerbating and perpetuating organ-restricted autoimmune diseases.

Effects of experimental allergic encephalomyelitis on thymus and adrenal: relation to remission and relapse.

AbstractExperimental allergic encephalomyelitis (EAE) was induced by active immunization with neural tissue and adjuvants and by passive transfer of living lymphoid cells. Severe thymolysis occurred along with severe clinical signs and lesions. Thymolysis was preceded and accompanied by a striking rise in serum corticosterone. Clinical signs then remitted, followed by a decline in serum corticosterone and beginning regeneration of the thymus, but histologic EAE lesions persisted. Adrenalectomy performed early in the remission of EAE was followed promptly by disappearance of serum corticosterone and relapses of clinical signs. Relapses occurred in rats of either sex but not until thymic regeneration had begun. All these data support the theory that nonspecific stress and the state of adrenal hyperactivity in response to neurological disability determine patterns of remission and relapse in EAE by way of immunosuppressive effects on lymphoid tissue.