Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity.
A variable region gene of the T-cell receptor, V beta 8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2u mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding V beta 8.2 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-gama. 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.
Waisman
A
A
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Ruiz
P J
PJ
Hirschberg
D L
DL
Gelman
A
A
Oksenberg
J R
JR
Brocke
S
S
Mor
F
F
Cohen
I R
IR
Steinman
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000276:immunology; D004247:DNA / Q000276:immunology*; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014612:Vaccines
D016207:Cytokines; D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014612:Vaccines; D004247:DNA