Abstract
Multiple sclerosis (MS) is an autoimmune disease mediated by myelin
autoantigen-specific T cells. Experimental autoimmune encephalomyelitis
(EAE) induced by immunization of mice with a myelin oligodendrocyte
glycoprotein (MOG) peptide emulsified in killed Mycobacterium
tuberculosis-containing complete Freund’s adjuvant (CFA-EAE) is
frequently used as a model of MS. Mycobacterium bovis BCG, a
vaccine strain with various biological response modifier activity, has
been reported to ameliorate clinical symptoms of the CFA-EAE although
precise mechanism has not yet been documented. Since the CFA-EAE uses
adjuvant with mycobacterial antigens, it is possible that mycobacterial
antigen-specific T cells induced by CFA and those by therapeutic BCG
inoculation recognize same antigens, and the cross-reactivity modulate
the EAE. To exclude the influence of the cross-reactivity, we
established a modified murine EAE model (CWS-EAE) which does not induce
mycobacterial antigen-specific T cells. Inoculation of BCG 6 days after
the CWS-EAE induction successfully ameliorated EAE symptoms, suggesting
the therapeutic effects of BCG is independent of the mycobacterial
antigen-specific T cells induced by CFA-EAE protocol. With the CWS-EAE
model, we confirmed that induction of MOG-specific Th17 in the spleen
and central nervous system (CNS) decreased with disappearance of
demyelination lesions by the BCG inoculation. The amelioration of CNS
pathology was not linked to changes in the number of macrophages,
neutrophil and conventional dendritic cells (DC) but associated with
decrease of plasmacytoid DC in CNS. The results suggest that BCG
inoculation suppress both systemic and CNS Th17 response in the EAE mice
and the mechanism may involve modulation of plasmacytoid DC.