Type I diabetes and multiple sclerosis patients target islet plus central nervous system autoantigens; nonimmunized nonobese diabetic mice can develop autoimmune encephalitis.
Type I diabetes and multiple sclerosis (MS) are distinct autoimmune diseases where T cells target either islet or CNS self-proteins. Unexpectedly, we found that autoreactive T cells in diabetic patients, relatives with high diabetes risk, nonobese diabetic (NOD) mice, and MS patients routinely target classical islet as well as CNS autoantigens. The pathogenic potential of CNS autoreactivity was testable in NOD mice. Pertussis holotoxin, without additional Ags or adjuvants, allowed development of an NOD mouse-specific, autoimmune encephalitis with variable primary-progressive, monophasic, and relapsing-remitting courses. T cells from diabetic donors transferred CNS disease to pertussis toxin-pretreated NOD.scid mice, with accumulation of CD3/IFN-gamma transcripts in the brain. Diabetes and MS appear more closely related than previously perceived. NOD mouse-specific, autoimmune encephalitis provides a new MS model to identify factors that determine alternative disease outcomes in hosts with similar autoreactive T cell repertoires.
Winer
S
S
The Hospital For Sick Children, St. Michael's Hospital, University of Toronto, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Ontario, Canada.
Astsaturov
I
I
Cheung
R
R
Gunaratnam
L
L
Kubiak
V
V
Cortez
M A
MA
Moscarello
M
M
O'Connor
P W
PW
McKerlie
C
C
Becker
D J
DJ
Dosch
H M
HM
D000208:Acute Disease; D019264:Adoptive Transfer; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008814:Mice, Inbred NZB; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D011446:Prospective Studies; D012008:Recurrence; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D016207:Cytokines; D004676:Myelin Basic Protein