The Involvement of Calpain in CD4+T Helper Cell Bias in Multple Sclerosis.
The pathogenesis of multiple sclerosis (MS) is mediated by massive infiltration of myelin-specific T cells into the central nervous system (CNS). Self-reactive CD4+T helper (Th) cells, specifically Th1 and Th17 cells, are hallmarks of active disease in progression, whereas Th2 cells are predominately in remission stages. Calpain has been shown to be upregulated in the CNS of MS patients and inhibition of calpain has been shown previously to decrease disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We investigated calpain involvement in Thcell bias. Here, we show that calpain inhibition in primary myelin basic protein (MBP) Ac1-11-specific T cells and MBP-specific T cell line cultures increase Th2 proliferation, cytokine profile, and transcription and signaling molecules. We also show a relative decrease in Th1 inflammatory factors in these same categories and a relative decrease in Th17 proliferation. These studies provide insight into the various roles that calpain plays in Th cell bias and proliferation and increases our understanding of the role that T cells play in the pathophysiology of EAE and MS. Results also indicate the mechanisms involved by which calpain inhibitor decreases the disease signs of EAE, suggesting that calpain inhibitor can be a possible therapeutic agent for the treatment of EAE and MS.
Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, South Carolina, SC 29425, USA ; Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 173 Ashley Avenue, South Carolina, SC 29425, USA.
Nicole
N
Trager
Vanderbilt Neurosciences, Vanderbilt University, 1211 Medical Center Dr, Nashville, TN 37232, USA.
Jonathan T
JT
Butler
Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, 173 Ashley Avenue, South Carolina, SC 29425, USA.
Azizul
A
Haque
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA.
Swapan K
SK
Ray
Department of Drug Discovery and Biomedical Science, Medical University of South Carolina, 280 Calhoun Street, Charleston, SC 29425, USA.
Craig
C
Beeson
Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, South Carolina, SC 29425, USA.
Naren L
NL
Banik
Calpain; Cytokines; EAE; Multiple sclerosis; STAT; T helper cells