Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). While etiology of the disease remains unknown, genetic susceptibility and autoimmune mechanisms in the initiation and progression of the disease have been strongly suggested. Experimental autoimmune encephalomyelitis (EAE) is commonly used to study immune regulation of MS. Infiltration by CD4+ T cells, through blood-brain barrier (BBB), precedes the onset and relapses of MS. CNS migration and homing patterns of T cells are tightly synchronized by astrocyte and microglia derived cytokines and chemokines. Autoimmune, CNS antigenreactive, infiltrating T cells produce and locally release cytokines including but not limited to IFNγ, IL-2, IL-6, IL-16, IL-17, TNFα, and chemokines including CCL2, CCL5 and CXCL10. Chemokine mediated chemotaxis is exclusive for activated cell state and most chemokines do not discriminate between distinct cell types. Conversely, a cytokine IL-16 is a CD4-specific cytokine-ligand and exclusively induces chemotaxis of CD4+T cells, by binding and signaling through CD4, regardless of T cell activation state. In this article we focus on CD4+ T cell-mediated autoimmune responses to CNS antigens because of their importance for immunopathology of MS and EAE. We focus on autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) because of its relevance for immunopathology of MS. We emphasize a role of IL-16 in regulation of CD4+T cell mediated autoimmune responses to MOG in EAE and MS. While a role of IL-16 in regulation of other CD4+T cell mediated autoimmune diseases has been established, its role in regulation of MS remains to be determined. Emerging data from our laboratories have indicated that IL-16-mediated CD4+ T cell chemoattraction has a significant role in regulation of CD4+ T cell-mediated autoimmune responses to CNS antigens. We propose an important function of this cytokine in regulation of relapsing-remitting EAE.
Tse HY, Skundric DS, Cruikshank WW, Montgomery PC, Lisak RP (2013) Immunopathology of CD4+ T Cell-Mediated Autoimmune Responses to Central Nervous System Antigens: Role of IL-16. J Immunol Clin Res 1:1006. http://www.jscimedcentral.com/Immunology/Articles/immunology-1-1006.php#tab. Accessed May 19, 2015.