This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rohowsky-Kochan, C Articles by Cook, S D Search for Related Content PubMed PubMed Citation Articles by Rohowsky-Kochan, C Articles by Cook, S D Social Bookmarking                   What's this?

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

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. G. Mujtaba, L. O. Flowers, C. B. Patel, R. A. Patel, M. I. Haider, and H. M. Johnson Treatment of Mice with the Suppressor of Cytokine Signaling-1 Mimetic Peptide, Tyrosine Kinase Inhibitor Peptide, Prevents Development of the Acute Form of Experimental Allergic Encephalomyelitis and Induces Stable Remission in the Chronic Relapsing/Remitting Form J. Immunol., October 15, 2005; 175(8): 5077 - 5086. [Abstract] [Full Text] [PDF]

				R. Fritsch, D. Eselbock, K. Skriner, B. Jahn-Schmid, C. Scheinecker, B. Bohle, M. Tohidast-Akrad, S. Hayer, J. Neumuller, S. Pinol-Roma, et al. Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis J. Immunol., July 15, 2002; 169(2): 1068 - 1076. [Abstract] [Full Text] [PDF]