Fulminant experimental autoimmune encephalo-myelitis induced by retrovirally mediated TCR gene transfer

Eur J Immunol. 2005 Jun;35(6):1822-30. doi: 10.1002/eji.200526123.

Abstract

Although some efforts have been made to direct the antigen specificity of developing T cells by retroviral mediated expression of known TCR, it is not clear if the resultant T cells are fully functional. In this study retroviral gene transfer technology was used to introduce a cDNA encoding the TCR from a known encephalitogenic T cell into the bone marrow of mice. Activated T cells expressing this TCR, which is specific for the Ac1-11 peptide from myelin basic protein presented by I-A(u), cause rapid onset of experimental autoimmune encephalomyelitis (EAE). This enabled us to use the onset and progression of the disease as a direct measure of effector functions of T cells generated by this method. The data presented here show that recipients of bone marrow retrovirally transduced with this TCR rapidly develop full-blown EAE that results in paralysis. Therefore, retroviral TCR delivery into the bone marrow supports the development of T cells into fully functional effector cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Gene Transfer, Horizontal*
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Mice
  • Myelin Basic Protein / immunology
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / physiology
  • Retroviridae / genetics
  • Spleen / immunology
  • T-Lymphocytes / physiology
  • Transduction, Genetic

Substances

  • Myelin Basic Protein
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Interferon-gamma