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Autoreactive T and B cells in nervous system diseases
1Department of Neurology, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Acta Neurologica Scandinavica. Supplementum
|January 1, 1993
Summary
Autoimmune T and B cells targeting myelin proteins are elevated in multiple sclerosis (MS) patients, particularly in cerebrospinal fluid (CSF). These responses, also seen in myasthenia gravis, are heightened after nerve trauma and in newborns.
Area of Science:
- Neuroimmunology
- Autoimmunity
- Cellular Immunology
Background:
- Abnormal autoimmunity is implicated in multiple sclerosis (MS) pathogenesis, analogous to experimental allergic encephalomyelitis (EAE).
- The presence and significance of T and B cell responses to myelin autoantigens (MBP, PLP, MOG, MAG) in MS, particularly in CSF, remain unclear.
- Autoimmune responses to acetylcholine receptor (AChR) in myasthenia gravis and the impact of nerve trauma on MS autoimmunity require investigation.
Purpose of the Study:
- To investigate antigen-specific T and B cell reactivity to myelin proteins and AChR in MS and myasthenia gravis.
- To determine the localization of these autoimmune responses in blood and cerebrospinal fluid (CSF).
- To assess the influence of nerve trauma and cord blood on autoimmune T and B cell repertoires.
Main Methods:
- Antigen-specific T cell responses were assessed by quantifying interferon-gamma (IFN-gamma) secreting cells post-stimulation.
- B cell responses were evaluated by counting antigen-specific antibody (IgG, IgA, IgM) secreting cells.
- Studies were conducted on blood and CSF samples from patients with MS, myasthenia gravis, other neurological diseases, tension headache, healthy subjects, and cord blood.
Main Results:
- MS patients exhibit elevated T and B cells recognizing myelin proteins (MBP, PLP, MOG, MAG), with significant enrichment in CSF.
- Myasthenia gravis patients show increased AChR and alpha-subunit reactive T cells and anti-AChR antibody-secreting cells.
- Nerve trauma transiently elevates T cells recognizing myelin proteins; these responses are also present at lower levels in healthy individuals and newborns.
Conclusions:
- Antigen-specific T cells targeting myelin proteins are a consistent finding in MS, with marked enrichment in CSF.
- Most myasthenia gravis patients demonstrate increased T and B cell reactivity to AChR.
- While present in healthy subjects, autoimmune T and B cell responses are augmented following nerve trauma and in newborns, suggesting a dynamic repertoire.