Local delivery of TNF by retrovirus-transduced T lymphocytes exacerbates experimental autoimmune encephalomyelitis

Clin Immunol. 1999 Jan;90(1):10-4. doi: 10.1006/clim.1998.4653.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. Paralysis is "induced" by CD4+ T cells of the Th1 phenotype. Tumor necrosis factor (TNF), a Th1 type cytokine, has been shown to be upregulated in the CNS during the onset of EAE, and systemic manipulations of TNF have had substantial effects on disease progression. However, the precise role of TNF in EAE has been called into question by recent experiments utilizing TNF and lymphotoxin knockout mice. We demonstrate here that the local delivery of TNF by myelin basic protein (MBP)-specific T cells, retrovirally transduced to express TNF, exacerbated MBP-induced disease following adoptive transfer into syngeneic mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Central Nervous System / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Female
  • Genetic Vectors
  • Guinea Pigs
  • Male
  • Mice
  • Myelin Basic Protein / genetics
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*
  • Transduction, Genetic
  • Tumor Necrosis Factor-alpha / administration & dosage*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Myelin Basic Protein
  • Tumor Necrosis Factor-alpha