The role of CTLA-4 in tolerance induction and T cell differentiation in experimental autoimmune encephalomyelitis: i.p. antigen administration.
Recent evidence suggests that co-stimulation provided by B7 molecules through CTLA-4 is important in establishing peripheral tolerance. In the present study, we examined the kinetics of tolerance induction and T cell differentiation following i.p. 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 response after antigen administration demonstrated a dependence on CTLA-4 for i.p. tolerance induction. Examination of splenocyte responses suggested that i.p. antigen administration induced a T(h)2 response, which was potentiated by anti-CTLA-4 administration. Interestingly, i.p. tolerance was able to inhibit the induction of experimental autoimmune encephalomyelitis and anti-CTLA-4 administration did not alter this phenotype, suggesting that CTLA-4 blockade did not block tolerance induction. Thus, T cell differentiation and the dependence on CTLA-4 for tolerance induction following i.p. antigen administration differs between lymph node and spleen in a model of organ-specific autoimmunity.
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 / Q000502:physiology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007108:Immune Tolerance; D018796:Immunoconjugates; D007274:Injections, Intraperitoneal; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000276:immunology; D010047:Ovalbumin / 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; D010047:Ovalbumin