Vaccination with BV8S2 protein amplifies TCR-specific regulation and protection against experimental autoimmune encephalomyelitis in TCR BV8S2 transgenic mice.
TCR determinants overexpressed by autopathogenic Th1 cells can naturally induce a second set of TCR-specific regulatory T cells. We addressed the question of whether immune regulation could be induced naturally in a genetically restricted model in which a major portion of TCR-specific regulatory T cells expressed the same target TCR BV8S2 chain as the pathogenic T cells specific for myelin basic protein (MBP). We found vigorous T cell responses to BV8S2 determinants in naive mice that could be further potentiated by vaccination with heterologous BV8S2 proteins, resulting in the selective inhibition of MBP-specific Th1 cells and protection against experimental encephalomyelitis. Moreover, coculture with BV8S2-specific T cells or their supernatants reduced proliferation, IFN-gamma secretion, and encephalitogenic activity of MBP-specific T cells. These results suggest that immune regulation occurs through a nondeletional cytokine-driven suppressive mechanism.
Offner
H
H
Portland Veterans Affairs Medical Center, Department of Neurology, Oregon Health Sciences University 97201, USA. offner.halina@portland.va.gov
Adlard
K
K
Bebo
B F
BF
Schuster
J
J
Burrows
G G
GG
Buenafe
A C
AC
Vandenbark
A A
AA
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019076:Transgenes / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005620:Freund's Adjuvant