Decreased expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 reduces T cell activation threshold but not the severity of experimental autoimmune myasthenia gravis.
Myasthenia gravis (MG) and its murine model experimental autoimmune myasthenia gravis (EAMG) are T cell-dependent, antibody-mediated autoimmune diseases. Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a cytosolic tyrosine phosphatase that is involved in regulating the T cell activation cascade from signals initiated through the TCR. To study the role of SHP-1 in EAMG pathogenesis, we immunized C57BL/6 (B6) mice heterozygous for deletion of the SHP-1 gene (me(v+/-)) and their littermate wild type B6 mice with torpedo acetylcholine receptor (TAChR). T cell proliferation and IFNgamma production were significantly increased in B6.me(v+/-) mice after immunization with AChR compared to that of wild type littermates. However, clinical incidence and severity of the disease were not changed. There also were no significant differences in AChR-specific antibodies produced between wild type and me(v+/-) mice. These data suggest that deficiency in SHP-1 expression does decrease the activation threshold of autoreactive T cells in EAMG, but the increased frequency of autoreactive T cells does not aggravate EAMG in terms of clinical score, incidence, or antibody titers.
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9036, USA.
Caishu
C
Deng
Bo
B
Wu
Huan
H
Yang
Rehana Z
RZ
Hussain
Amy E
AE
Lovett-Racke
Premkumar
P
Christadoss
Michael K
MK
Racke
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D018909:src Homology Domains / Q000235:genetics
D001323:Autoantibodies; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D047908:Intracellular Signaling Peptides and Proteins; D011950:Receptors, Cholinergic; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse