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Cytokine secretion profile of myelin basic protein-specific T cells in multiple sclerosis

Department of Neurosciences, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey, NJ 07103, USA

D Molinaro

Department of Neurosciences, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey, NJ 07103, USA

S D Cook

Department of Neurosciences, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey, NJ 07103, USA

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a presumed autoimmune pathogenesis involving autoantigen-specific CD4⁺ T cells and cytokines. A similar frequency of T cells responding to myelin basic protein (MBP), a putative target in MS, has been observed in MS patient and controls. To dissect the differences between MBP-specific T cells in patient and controls, we have analyzed the cytokine secretion profile of such autoreactive T cells. MBP-specific T cell clones (TCC) were isolated from the peripheral blood of MS patient and controls by limiting dilution. Expression of mRNA for interferon- (IFN-), interleukin (IL)-4, IL-10, tumor necrosis factor- (TNF-) and transforming growth factor-ß (TGF-ß) was assessed by polymerase chain reaction whereas secretion of cytokine protein was measured by ELISA. MBP-specific TCC exhibited a heterogeneous cytokine secretion profile with clones displaying Th1, Th2 and Th0 phenotypes. A significant difference in the distribution of the cytokine profile was noted between MS patients and controls. Although the frequency of Th1 secreting MBP-reactive TCC was similar between MS patients and controls, stable MS patient had a significant association with the Th0 phenotype whereas healthy individuals were associated with the Th2 phenotype. In comparison to control TCC, MBP-specific TCC from MS patients secreted increased amount of IFN-, IL-4 and IL-10 and decreased quantities of TGF-ß. Thus, these studies suggest that there is a dysregulation in the balance between pro-inflammatory Th1 and anti-inflammatory Th2 cytokines in MS. It appears that the presence of Th1 secreting autoreactive T cells in healthy individuals may be counterbalanced by the presence of cells secreting Th2 cytokines and by the augmented production of the immunosuppressive cytokine TGF-ß, whereas in MS there is a decrease in these anti-inflammatory agents.

Key Words: autoantigen-specific T cells • Th1/Th2 cytokines • multiple sclerosis

Multiple Sclerosis, Vol. 6, No. 2, 69-77 (2000)
DOI: 10.1177/135245850000600203


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