More MS news articles for April 2002

Expression of the tyrosine phosphatase SRC homology 2 domain-containing protein tyrosine phosphatase 1 determines T cell activation threshold and severity of experimental autoimmune encephalomyelitis

J Immunol 2002 May 1;168(9):4511-8
Deng C, Minguela A, Hussain RZ, Lovett-Racke AE, Radu C, Ward ES, Racke MK.
Department of Neurology, Center for Immunology, and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390.

Experimental autoimmune encephalomyelitis (EAE) is a CD4 Th1-mediated inflammatory demyelinating disorder of the CNS and a well-established animal model for multiple sclerosis.

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 EAE pathogenesis, we immunized B10.PL mice heterozygous for deletion of the SHP-1 gene (me(v+/-)) and B10.PL wild-type mice with the immunodominant epitope of myelin basic protein (MBP Ac1-11).

T cell proliferation and IFN-gamma production were significantly increased in me(v+/-) mice after immunization with MBP Ac1-11.

The frequency of MBP Ac1-11-specific CD4 T cells, analyzed by staining with fluorescently labeled tetramers (MBP1-11[4Y]: I-A(u) complexes), was increased in the draining lymph node cells of me(v+/-) mice compared with wild-type mice.

In addition, me(v+/-) mice developed a more severe course of EAE with epitope spreading to proteolipid protein peptide 43-64.

Finally, expansion of MBP Ac1-11-specific T cells in response to Ag was enhanced in me(v+/-) T cells, particularly at lower Ag concentrations.

These data demonstrate that the level of SHP-1 plays an important role in regulating the activation threshold of autoreactive T cells.