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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

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
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

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 (mev+/-) and B10.PL wild-type mice with the immunodominant epitope of myelin basic protein (MBP Ac1-11). T cell proliferation and IFN-γ production were significantly increased in mev+/- 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-Au complexes), was increased in the draining lymph node cells of mev+/- mice compared with wild-type mice. In addition, mev+/- 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 mev+/- 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.

0022-1767
4511-4518
Deng, Caishu
5b0a7d97-b196-4217-8503-211bfd065685
Minguela, Alfredo
89d0d2bb-fdfb-47ad-b925-4c0687ede7ae
Hussain, Rehana Z.
0251b80a-13f2-4754-83e0-d785b749f59d
Lovett-Racke, Amy E.
fab15e80-d854-4afd-be5e-1cffbb4f2d36
Radu, Caius
cf50ccf6-c03c-4d8f-abd8-56681251f990
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Racke, Michael K.
fd372156-c5df-402d-82de-8ecc3a4bce3f
Deng, Caishu
5b0a7d97-b196-4217-8503-211bfd065685
Minguela, Alfredo
89d0d2bb-fdfb-47ad-b925-4c0687ede7ae
Hussain, Rehana Z.
0251b80a-13f2-4754-83e0-d785b749f59d
Lovett-Racke, Amy E.
fab15e80-d854-4afd-be5e-1cffbb4f2d36
Radu, Caius
cf50ccf6-c03c-4d8f-abd8-56681251f990
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Racke, Michael K.
fd372156-c5df-402d-82de-8ecc3a4bce3f

Deng, Caishu, Minguela, Alfredo, Hussain, Rehana Z., Lovett-Racke, Amy E., Radu, Caius, Ward, E. Sally and Racke, Michael K. (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. Journal of Immunology, 168 (9), 4511-4518. (doi:10.4049/jimmunol.168.9.4511).

Record type: Article

Abstract

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 (mev+/-) and B10.PL wild-type mice with the immunodominant epitope of myelin basic protein (MBP Ac1-11). T cell proliferation and IFN-γ production were significantly increased in mev+/- 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-Au complexes), was increased in the draining lymph node cells of mev+/- mice compared with wild-type mice. In addition, mev+/- 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 mev+/- 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.

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Accepted/In Press date: 5 March 2002
Published date: 1 May 2002

Identifiers

Local EPrints ID: 425141
URI: http://eprints.soton.ac.uk/id/eprint/425141
ISSN: 0022-1767
PURE UUID: 907a8c61-d1b7-4874-9b99-8adc73cb8457
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 11 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Caishu Deng
Author: Alfredo Minguela
Author: Rehana Z. Hussain
Author: Amy E. Lovett-Racke
Author: Caius Radu
Author: E. Sally Ward ORCID iD
Author: Michael K. Racke

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