The role of CTLA-4 in tolerance induction and ttigen administration cell differentiation in experimental autoimmune encephalomyelitis: i. v. antigen administration.
Interactions between B7 molecules on antigen-presenting cells and CTLA-4 on T cells have been shown to be important in establishing tolerance. In the present study, we examined the kinetics of tolerance induction following i.v. administration of myelin basic protein (MBP) Ac1-11 in mice transgenic for a TCR V(beta)8.2 gene derived from an encephalitogenic T cell clone specific for MBP Ac1-11. Examination of the lymph node cell (LNC) response 10 days after antigen administration demonstrated an accentuation of i.v. tolerance induction with anti-CTLA-4 blockade. Anergy was induced in splenocytes by i.v. antigen administration as shown by a decrease in MBP-specific proliferation and IL-2 production, and anti-CTLA-4 potentiated this effect. In addition, i.v. antigen plus anti-CTLA-4 and complete Freund's adjuvant was not encephalitogenic. Interestingly, i.v. tolerance (a single injection) did not inhibit experimental autoimmune encephalomyelitis (EAE) and anti-CTLA-4 administration did not alter this phenotype. These results suggest that while the majority of MBP-specific T cells are tolerized by i.v. antigen and that this process is potentiated by anti-CTLA-4 administration, a population of T cells remains that is quite efficient in mediating EAE.
Ratts
R B
RB
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Arredondo
L R
LR
Bittner
P
P
Perrin
P J
PJ
Lovett-Racke
A E
AE
Racke
M K
MK
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007108:Immune Tolerance; D018796:Immunoconjugates; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000069594:Abatacept