ausblenden:
Schlagwörter:
T-CELL RESPONSES; MULTIPLE-SCLEROSIS; B-CELLS; TRANSGENIC MICE;
AUTOANTIBODIES; INDUCTION; BACTERIA; DISEASE; MOG
Zusammenfassung:
Active multiple sclerosis lesions show inflammatory changes suggestive
of a combined attack by autoreactive T and B lymphocytes against brain
white matter(1). These pathogenic immune cells derive from progenitors
that are normal, innocuous components of the healthy immune repertoire
but become autoaggressive upon pathological activation. The stimuli
triggering this autoimmune conversion have been commonly attributed to
environmental factors, in particular microbial infection(2). However,
using the relapsing-remitting mouse model of spontaneously developing
experimental autoimmune encephalomyelitis(3), here we show that the
commensal gut flora-in the absence of pathogenic agents-is essential in
triggering immune processes, leading to a relapsing-remitting autoimmune
disease driven by myelin-specific CD4(+) T cells. We show further that
recruitment and activation of autoantibody-producing B cells from the
endogenous immune repertoire depends on availability of the target
autoantigen, myelin oligodendrocyte glycoprotein (MOG), and commensal
microbiota. Our observations identify a sequence of events triggering
organ-specific autoimmune disease and these processes may offer novel
therapeutic targets.
