Gender differences in protection from EAE induced by oral tolerance with a peptide analogue of MBP-Ac1-11.
Mechanisms that contribute to increased female susceptibility to multiple sclerosis can be studied in the murine model of experimental autoimmune encephalomyelitis (EAE). In this report, we compared oral tolerance induction in male and female B10.PL mice using fed myelin basic protein (MBP) Ac1-11 peptide or a high-affinity analogue, Ac1-11[4Y]. We found that fed Ac1-11[4Y] peptide, but not native Ac1-11, could limit cellular infiltration into the central nervous system (CNS) and protect male mice from EAE, an effect that was completely obviated by castration. In contrast, female mice could not be orally tolerized or protected from EAE with either peptide. Tolerance induction in males was reflected by the appearance of Ac1-11[4Y]-reactive splenocytes that produced a sharply increased ratio of transforming growth factor (TGF)-beta:interleukin (IL)-2 and induced bystander suppression. These data directly demonstrate gender differences in regulatory T cells, and support the concept that androgens are involved in governing oral tolerance to EAE.
Bebo
B F
BF
Department of Neurology, Oregon Health Sciences University, Portland, USA.
Adlard
K
K
Schuster
J C
JC
Unsicker
L
L
Vandenbark
A A
AA
Offner
H
H
D000284:Administration, Oral; D000818:Animals; D002369:Castration; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D012737:Sex Factors; D013116:Spinal Cord / Q000166:cytology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000187:drug effects
D007376:Interleukin-2; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C405722:myelin basic protein 1-11; C074815:myelin basic protein 1-9; C405723:myelin basic protein Ac1-11(4Y)