Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity

Ari Waisman, Pedro J. Ruiz, David L. Hirschberg, Avraham Gelman, Jorge R. Oksenberg, Stefan Brocke, Felix Mor, Irun R. Cohen, Lawrence Steinman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

230 Scopus citations

Abstract

A variable region gene of the T-cell receptor, Vβ8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2(u) mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding Vβ8.2 protected mice from EAE. Analysis of T cells reacting to the pathogenic portion of the MBP molecule indicated that in the vaccinated mice there was a reduction in the Th1 cytokines interleukin-2 (IL-2) and interferon-γ. In parallel, there was an elevation in the production of IL- 4, a Th2 cytokine associated with suppression of disease. A novel feature of DNA immunization for autoimmune disease, reversal of the autoimmune response from Th1 to Th2, may make this approach attractive for treatment of Th1- mediated diseases like multiple sclerosis, juvenile diabetes and rheumatoid arthritis.

Original languageEnglish
Pages (from-to)899-905
Number of pages7
JournalNature Medicine
Volume2
Issue number8
DOIs
StatePublished - 1996
Externally publishedYes

Funding

FundersFunder number
National Institute of Neurological Disorders and StrokeR01NS018235

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