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-gamma 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 gamma/delta 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.
Birnbaum
G
G
Department of Neurology, University of Minnesota, Minneapolis, USA. birnb001@tc.umn.edu
Kotilinek
L
L
Miller
S D
SD
Raine
C S
CS
Gao
Y L
YL
Lehmann
P V
PV
Gupta
R S
RS
D000818:Animals; D016516:CD4-CD8 Ratio; D018834:Chaperonin 60 / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012008:Recurrence; D013047:Specific Pathogen-Free Organisms
D018834:Chaperonin 60; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta