Cytokine profile of myelin basic protein—reactive T cells in multiple sclerosis and healthy individuals

Abstract

Myelin basic protein (MBP)-reactive T cells have been implicated in the autoimmune pathogenesis of multiple sclerosis (MS). In this study, we examined the cytokine profile of 531 primary MBP-reactive T-cell lines and 72 independently established clones from 32 patients with MS and 18 healthy controls (NS) by using highly sensitive enzyme-linked immunosorbent assays. An increased number of primary T-cell lines producing interferon-gamma (IFN gamma) and/or interleukin-4 (IL-4) in response to MBP were found in patients with MS compared with controls. No distinct Th1 or Th2 subtypes could be demonstrated among the MBP-reactive clones. IL-4 was more frequently observed among MS-derived clones. Clones derived from MS patients produced increased levels of IL-2, IL-4, tumor necrosis factor-alpha (TNF alpha), IFN gamma, and IL-10, but not IL-6. It is interesting that MBP-reactive T cells from MS patients expressing the disease-associated HLA-DRB1*15 allele produced increased quantities of TNF alpha, a cytokine suggested to play an important role in inflammation and demyelination. When challenged with either MBP or a bacterial superantigen, the clones expressed similar levels of the proinflammatory cytokine IFN gamma. Our study suggests a functional difference in T-cell responses to MBP in patients with MS compared with healthy individuals, and provides further insights into the role of MBP-reactive T cells and their cytokine profile in the inflammatory processes of MS.

Stable antigen‐specific T‐cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients

“…MS patients' autoreactive T cells are generally considered strong secretors of proinflammatory cytokines [36]. Interestingly, our results showed that T cells primed by tolDCs were refractory to further stimulation using myelin peptides-loaded APC, thus emphasizing the tolerogenic potential of tolDCs in MS patients.…”

The Human T Cell Response to Myelin Oligodendrocyte Glycoprotein: A Multiple Sclerosis Family-Based Study

“…High levels of TNF-␣ have been identified in MS brain lesions (58), and some reports indicate that levels of Th1 cytokines produced by PBMC (59 -62), by CSF (63), or by myelin-reactive TCC or lines (35,64) have also been associated with disease activity in MS. One analysis of cytokine secretion of 30 MBP-specific TCC revealed elevated IFN-␥:IL-4 ratios in MS patients (65). By contrast, other studies failed to demonstrate clear differences in cytokine profiles of MBP-reactive TCC or T cell lines between patients and controls (66,71).…”

Effects of TNF-α and IFN-γ on Nitric Oxide-Induced Neurotoxicity in the Mouse Brain

“…Agstimulated T cells have the ability to produce TNF-␣ along with IFN-␥ that acts in both innate and specific cell-mediated immunities (2). Activated CD4 ϩ Th1 cells and their secreted cytokines are believed to be crucial to the pathogenesis of multiple sclerosis, especially during the demyelinating episodes (3). The mixture of both TNF-␣ and IFN-␥ may therefore be harmful to neuronal elements.…”

“…Activation of the inducible form of NO synthase (iNOS) 3 and NO production take place during many neuropathological conditions (7). iNOS is responsible for the cytotoxic action of macrophages and neutrophils and NO has been implicated in neurodegeneration and chronic inflammation (8,9).…”