Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis
EJ Baughman, JP Mendoza, SB Ortega, CL Ayers… - Journal of …, 2011 - Elsevier
Journal of autoimmunity, 2011•Elsevier
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous
system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly
focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell
responses in MS patients and healthy subjects. However, the role of neuroantigen-specific
CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent
pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar …
system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly
focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell
responses in MS patients and healthy subjects. However, the role of neuroantigen-specific
CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent
pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar …
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell responses in MS patients and healthy subjects. However, the role of neuroantigen-specific CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar magnitudes of CD8+ and CD4+ T-cell responses to various antigenic stimuli. Interestingly, CD8+ T-cells specific for CNS autoantigens, but not those specific for control foreign antigens, exhibit immune regulatory ability, suppressing proliferation of CD4+CD25− T-cells when stimulated by their cognate antigen. While CD8+ T-cell-mediated immune suppression is similar between healthy subjects and clinically quiescent treatment-naïve MS patients, it is significantly deficient during acute exacerbation of MS. Of note, the recovery of neuroantigen-specific CD8+ T-cell suppression correlates with disease recovery post-relapse. These studies reveal a novel immune suppressor function for neuroantigen-specific CD8+ T-cells that is clinically relevant in the maintenance of peripheral tolerance and the intrinsic regulation of MS immune pathology.
Elsevier
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