Abstract
Because presentation of acetylcholine receptor (AChR) peptides to T cells is critical to the development of myasthenia gravis, we examined the role of cathepsin S (Cat S) in experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. Compared with wild type, Cat S null mice were markedly resistant to the development of EAMG, and showed reduced T and B cell responses to AChR. Cat S null mice immunized with immunodominant AChR peptides showed weak responses, indicating failed peptide presentation accounted for autoimmune resistance. A Cat S inhibitor suppressed in vitro IFN-gamma production by lymph node cells from AChR-immunized, DR3-bearing transgenic mice. Because Cat S null mice are not severely immunocompromised, Cat S inhibitors could be tested for their therapeutic potential in EAMG.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antigen Presentation / genetics
-
Antigen-Presenting Cells / immunology
-
Antigen-Presenting Cells / metabolism
-
Autoantibodies / blood
-
B-Lymphocytes / pathology
-
Cathepsins / antagonists & inhibitors
-
Cathepsins / deficiency
-
Cathepsins / genetics
-
Cathepsins / physiology*
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology
-
Cell Movement / genetics
-
Cell Movement / immunology
-
Cytokines / antagonists & inhibitors
-
Cytokines / biosynthesis
-
Dendritic Cells / cytology
-
Dendritic Cells / immunology
-
Down-Regulation / genetics
-
Down-Regulation / immunology
-
Epitopes, T-Lymphocyte / immunology
-
Female
-
HLA-DR3 Antigen / genetics
-
HLA-DR3 Antigen / immunology
-
HLA-DR3 Antigen / metabolism
-
Humans
-
Immunity, Innate / genetics
-
Lymphocyte Activation / genetics
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Myasthenia Gravis, Autoimmune, Experimental / enzymology*
-
Myasthenia Gravis, Autoimmune, Experimental / genetics
-
Myasthenia Gravis, Autoimmune, Experimental / immunology*
-
Peptide Fragments / immunology
-
Peptide Fragments / metabolism
-
Receptors, Cholinergic / administration & dosage
-
Receptors, Cholinergic / immunology
-
Receptors, Cholinergic / metabolism
-
T-Lymphocytes / immunology
-
T-Lymphocytes / metabolism
-
Torpedo
Substances
-
Autoantibodies
-
Cytokines
-
Epitopes, T-Lymphocyte
-
HLA-DR3 Antigen
-
Peptide Fragments
-
Receptors, Cholinergic
-
Cathepsins
-
cathepsin S