scholarly journals IL-12 unmasks latent autoimmune disease in resistant mice.

1996 ◽  
Vol 184 (2) ◽  
pp. 771-775 ◽  
Author(s):  
B M Segal ◽  
E M Shevach
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Immune Responses ◽  
Experimental Allergic Encephalomyelitis ◽  
Basic Protein ◽  
Inbred Mice ◽  
Allergic Encephalomyelitis ◽  
Ifn Gamma ◽  
Th 1 ◽  
Experimental Allergic

Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of the susceptible SJL (H-2s) and resistant B10.S (H-2s) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th 1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases.

scholarly journals Dual Role for Fas Ligand in the Initiation of and Recovery from Experimental Allergic Encephalomyelitis

1999 ◽  
Vol 189 (8) ◽  
pp. 1195-1205 ◽  
Author(s):  
Kimberly A. Sabelko-Downes ◽  
Anne H. Cross ◽  
John H. Russell
Keyword(s):  
T Cells ◽  
Experimental Allergic Encephalomyelitis ◽  
Fas Ligand ◽  
Basic Protein ◽  
Clinical Signs ◽  
Cell Receptor ◽  
Wild Type ◽  
Allergic Encephalomyelitis ◽  
Donor Cells ◽  
Experimental Allergic

We have previously demonstrated a role for Fas and Fas ligand (FasL) in the pathogenesis of experimental allergic encephalomyelitis (EAE). However, using an active induction paradigm we could not distinguish between FasL expressed on activated CD4+ T cells from that expressed on other inflammatory or resident central nervous system (CNS) cells. To address this issue, we have conducted reciprocal adoptive transfer experiments of nontransgenic or myelin basic protein–specific T cell receptor transgenic wild-type, lpr, or gld lymphocytes into congenic wild-type, lpr, and gld hosts. We found that FasL expressed on donor cells is important for the development of EAE, as FasL-deficient lymphocytes transfer attenuated disease. Furthermore, Fas expressed in the recipient animals is important for the progression of EAE, as clinical signs of disease in lpr recipients were dramatically attenuated after transfer of either wild-type or lpr T cells. Surprisingly, these experiments also identified CNS cells as a source of functional FasL. Host-derived FasL appears to be especially important in the recovery from EAE, as many gld recipients of wild-type lymphocytes develop prolonged clinical signs of disease. Thus it appears that FasL plays distinct roles in EAE during the initiation of and recovery from disease.

scholarly journals Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein.

1989 ◽  
Vol 169 (5) ◽  
pp. 1681-1691 ◽  
Author(s):  
J P Clayton ◽  
G M Gammon ◽  
D G Ando ◽  
D H Kono ◽  
L Hood ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
Myelin Basic Protein ◽  
Experimental Allergic Encephalomyelitis ◽  
Basic Protein ◽  
Disease Incidence ◽  
Cell Epitope ◽  
Allergic Encephalomyelitis ◽  
Significant Difference ◽  
Experimental Allergic

Experimental allergic encephalomyelitis (EAE) is a model of antigen-specific T cell-mediated autoimmune disease. The alpha-acetylated, NH2-terminal nine amino acids (1-9NAc) of myelin basic protein (MBP) represents the dominant T cell epitope for the induction of EAE in the B10.PL (H-2u) strain. We tolerized neonatal B10.PL mice to 1-9NAc and studied the proliferative responses to this peptide and to whole MBP. Mice exposed to 1-9NAc in the neonatal period were tolerant to subsequent challenge at the proliferative T cell level. Similarly, in the 1-9NAc-tolerant group, both the incidence and severity of 1-9NAc induced EAE were greatly reduced. The fact that we were able to tolerize mice normally responsive to MBP suggests that this self antigen is sequestered (within the central nervous system) and hence tolerance to it is not normally induced. No significant difference in disease incidence was seen in response to rat MBP between control animals and 1-9NAc-tolerized mice (50% in both groups), demonstrating the presence of at least one additional encephalitogenic determinant elsewhere on the molecule. We have successfully prevented disease induction by peptide-induced tolerization. Tolerance induction by peptides provides a new and specific strategy in the prevention of autoimmunity. However, it will be clearly necessary to fully define all epitopes potentially capable of inducing pathogenic T cells to ensure complete and effective therapy of T cell-mediated autoimmune disease.

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