Multiple sclerosis: Comparison of copolymer-1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells

Oliver Neuhaus, Cinthia Farina, Alexander Yassouridis, Heinz Wiendl, Florian Then Bergh, Tatjana Dose, Hartmut Wekerle, Reinhard Hohlfeld

Research output: Contribution to journalArticlepeer-review

Abstract

Copolymer 1 (COP), a standardized mixture of synthetic polypeptides consisting of L-glutamic acid, L-lysine, L-alanine, and L-tyrosine, has beneficial effects in multiple sclerosis and experimental autoimmune encephalomyelitis. We selected a panel of 721 COP-reactive T cell lines (TCL) from the blood of COP-treated and untreated multiple sclerosis patients and from healthy donors by using the split-well cloning technique. All TCL selected with COP proliferated in response to COP but not to myelin basic protein (MBP). Conversely, 31 control TCL selected with MBP proliferated in response to MBP but not to COP. We used intracellular double- immunofluorescence flow cytometry for quantitative analysis of cytokine production (IL-4, IFN-γ) by the TCL. The majority of the COP-reactive TCL from untreated multiple sclerosis patients and normal donors predominantly produced IFN-γ and, accordingly, were classified as T helper 1 cells (TH1). In contrast, the majority of the COP-reactive TCL from COP-treated patients predominantly (but not exclusively) produced IL-4-i.e., were TH2 (P <0.05 as assessed by using a suitable preference intensity index). Longitudinal analyses revealed that the cytokine profile of COP-reactive TCL tends to shift from TH1 to TH2 during treatment. Interestingly, although there was no proliferative cross-reaction, about 10% of the COP-reactive TCL responded to MBP by secretion of small amounts of IL-4 or IFN-γ, depending on the cytokine profile of the TCL. These results are consistent with a protective effect of COP-reactive TH2 cells. It is hypothesized that these cells are activated by COP in the periphery, migrate into the central nervous system, and produce immunomodulatory cytokines after local recognition of MBP.

Original languageEnglish
Pages (from-to)7452-7457
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number13
DOIs
Publication statusPublished - Jun 20 2000

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint

Dive into the research topics of 'Multiple sclerosis: Comparison of copolymer-1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells'. Together they form a unique fingerprint.

Cite this