The Role of CD8+ T Cells in Multiple Sclerosis and its Animal Models

Abstract

The role of CD8(+) T cells in multiple sclerosis (MS) and its animal models has been enigmatic. Most studies of MS have focused on the role of CD4(+) Th1 T cells and many therapeutic strategies have been directed toward ameliorating the activity of this subset. Some of these strategies were effective in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for MS dependent on CD4(+) T cells, but paradoxically have worsened disease in MS patients. A great deal of evidence suggests that CD8(+) T cells contribute to the pathogenesis of MS and should be considered in designing therapies. CD8(+) T cells outnumber CD4(+) T cells in MS lesions, and both clonal expansion and enrichment of memory cells is preferentially seen in the CD8(+) T cell subset in the brain and cerebrospinal fluid of MS patients. New animal models have been developed that employ myelin-specific CD8(+) T cells to induce central nervous system autoimmunity. In a CD8(+) T cell model targeting myelin basic protein, clinical signs and pathology distinct from CD4(+) T cell-mediated disease were observed that exhibited similarities to some aspects of MS. These differences are consistent with distinct effector mechanisms employed by CD8(+) and CD4(+) T cells in mediating tissue damage and suggest a need to consider the activity of CD8(+) T cells in drug design. This review will focus on our current understanding of the role of CD8(+) T cells in MS and the new animal models that allow us to investigate further the pathogenicity of this subset.

Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis

“…Furthermore, CD8 T cell responses are elicited after MOG protein immunization. MOG35-55 only contains one CD8 T cell epitope, whereas MOG protein contains several CD8 T cell epitopes [42]. TLR4 and TLR9 signaling may dampen these disease processes, although the observed enhanced serum IL-17 argues for a regulatory role of TLR4 during activation of Th17 cells.…”

Interferon‐β therapy reduces CD4+ and CD8+ T‐cell reactivity in multiple sclerosis

“…29 Recent studies indicate that the immune response in MS engages a broader range of immune cells, including CD8 + T cells and B lymphocytes, that target various brain antigens. [2][3][4]21,30,31 Even more, CD8 + T cells usually outnumber CD4 + T cells in the CNS Error bars indicate the mean values ± SEM for each group. *P < 0Á05; **P < 0Á01; ***P < 0Á001.…”

Central Nervous System Resident Cells in Neuroinflammation: A Brave New World.

“…Concerning its onset and evolution, MS may be separated in i) primary progressive ii) secondary progressive and also iii) the relapsing-remitting type. Usually the disease starts with a relapse-remitting pattern of the symptoms followed by a progressive stage of increasing disability, considered the more severe cases (Weiner 2008 MS was previously considered to be the prototype of a Th1 type of autoimmune disease, where IFN--secreting T CD4 (Kroenke MA 2007;Dardalhon V 2008) and CD8 (Michael P. Crawford 2004;Goverman J 2005) cells are greatly relevant and widely found in the periphery, liquor and brain parenchyma (Matusevicius D 1999). On the other hand, many contrasting data were obtained using the EAE model.…”