In vitro modulation of human, autoreactive MBP-specific CD4 + T-cell clones by cyclosporin A

Martin Pette, Dagmar F. Pette, Paolo A. Muraro, Roland Martin, Henry F. McFarland

Research output: Contribution to journalArticle

Abstract

Cyclosporin A (CsA) is a potent immunosuppressant affecting many components of cellular and humoral immunity. Its main action probably results from inhibition of T-lymphocyte activation and interference with secretion of cytokines like IL-2, IL-4, IFN-γ and TNF-α. Correspondingly, CsA has beneficial effects on the course of several autoimmune diseases thought to be mediated by T-lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4 + cytotoxic T-lymphocytes specific for myelin basic protein, a putative target autoantigen in MS, to CsA in vitro, and determined the drug's effects on proliferation, expression of high affinity IL-2R, secretion of the proinflammatory cytokines IFN-γ and TNF-α as well as on the secretion of the chemokines MIP-1α and MIP- 1β. In all instances, we observed a partial to complete inhibition. In contrast, the response of activated cells to IL-2 was resistant to CsA. Our observations are in line with results obtained in different experimental systems. The discrepancy between the profound inhibition of T-cells and the modest therapeutic effects on MS is discussed.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalJournal of Neuroimmunology
Volume76
Issue number1-2
DOIs
StatePublished - Jun 1997
Externally publishedYes

Keywords

  • Cyclosporin A
  • In vitro
  • Multiple sclerosis
  • T-lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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