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

Multiple sclerosis (MS) is a demyelinating disease of the central nervous s ystem with a presumed autoimmune pathogenesis involving outoontigenspecific 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 patients and controls. To dissect the differences between MBP-specific T cells in patients and controls, we have analyzed the cytokine secretion pr ofile of such autoreactive T cells. MBP-specific T cell clones (TCC) were i solated from the peripheral blood of MS patients and controls by limiting d ilution. Expression of mRNA for interferon-gamma (IFN-gamma), interleukin ( IL)-4, IL-10, tumor necrosis factor-alpha (TNF-alpha) and transforming grow th factor-beta (TGF-beta) was assessed by polymerase chain reaction whereas secretion of cytokine protein was measured by ELISA. MBP-specific TCC exhi bited a heterogeneous cytokine secretion profile with clones displaying Th1 , Th2 and Th0 phenotypes. A significant difference in the distribution of t he cytokine profile was noted between MS patients and controls. Although th e frequency of Th1 secreting MBP-reactive TCC was similar between MS patien ts and controls, stable MS patients had a significant association with the Th0 phenotype whereas healthy individuals were associated with the Th2 phen otype. In comparison to control TCC, MBP-specific TCC from MS patients secr eted increased amounts of IFN-gamma, IL-4 and IL-10 and decreased quantitie s of TGF-beta. Thus, these studies suggest that there is a dysregulation in the balance between proinflammatory Th1 and anti-inflammatory Th2 cytokine s in MS. It appears that the presence of Th1 secreting outoreactive T cells in healthy individuals may be counterbalanced by the presence of cells sec reting Th2 cytokines and by the augmented production of the immunosuppressi ve cytokine TGF-beta, whereas in MS there is a decrease in these anti-infla mmatory agents.