Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation.
Usually we rely on vaccination to promote an immune response to a pathogenic microbe. In this study, we demonstrate a suppressive from of vaccination, with DNA encoding a minigene for residues 139-151 of myelin proteolipid protein (PLP139-151), a pathogenic self-Ag. This suppressive vaccination attenuates a prototypic autoimmune disease, experimental autoimmune encephalomyelitis, which presents clinically with paralysis. Proliferative responses and production of the Th1 cytokines, IL-2 and IFN-gamma, were reduced in T cells responsive to PLP139-151. In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN-gamma were reduced. A mechanism underlying the reduction in severity and incidence of paralytic autoimmune disease and the reduction in Th1 cytokines involves altered costimulation of T cells; loading of APCs with DNA encoding PLP139-151 reduced the capacity of a T cell line reactive to PLP139-151 to proliferate even in the presence of exogenous CD28 costimulation. DNA immunization with the myelin minigene for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in the spleen. Suppressive immunization against self-Ags encoded by DNA may be exploited to treat autoimmune diseases.
Ruiz
P J
PJ
Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, CA 94305, USA.
Garren
H
H
Ruiz
I U
IU
Hirschberg
D L
DL
Nguyen
L V
LV
Karpuj
M V
MV
Cooper
M T
MT
Mitchell
D J
DJ
Fathman
C G
CG
Steinman
L
L
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D001324:Autoantigens; D007166:Immunosuppressive Agents; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D019444:Vaccines, DNA; C435023:myelin proteolipid protein (139-151)