Journal of Clinical and Cellular Immunology
Open Access

Abstract

Regulation of Encephalitogenicity of Neuroantigen-Primed T Cells by Nitric Oxide: Implications for Multiple Sclerosis

Susanta Mondal, Saurav Brahmachari and Kalipada Pahan

Neuroantigen-specific T cells play an important role in the disease process of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). These cells are encephalitogenic and in susceptible animals, these cells alone can cause EAE. However, mechanisms by which encephalitogenicity is controlled are poorly understood. This study underlines the importance of nitric oxide (NO) in the regulation of encephalitogenicity of T cells. Interestingly, reducing NO during myelin basic protein (MBP)- priming of T cells attenuated the ability of these T cells to induce EAE and EAE-associated neuroinflammation and demyelination. Consistently, increasing NO had opposite effect. Similarly scavenging NO reduced the encephalitogenicity of PLP-specific T cells isolated from female PLP-TCR transgenic mice and supplementation of NO broke the tolerance of PLP-specific T cells of male PLP-TCR mice. Reduced encephalitogenicity of neuroantigen-primed T cells isolated from iNOS (-/-) mice compared to that from wild type mice clearly defines an essential role of iNOS-derived NO in controlling the encephalitogenicity of myelin-specific T cells. This study illustrates a novel role of NO in controlling encephalitogenicity of T cells that may participate in the complex pathogenesis of MS.