C. Garrison Fathman

Publication Details

  • Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: Modulation of T cell costimulation JOURNAL OF IMMUNOLOGY Ruiz, P. J., Garren, H., Ruiz, I. U., Hirschberg, D. L., Nguyen, L. V., Karpuj, M. V., Cooper, M. T., Mitchell, D. J., Fathman, C. G., Steinman, L. 1999; 162 (6): 3336-3341

    Abstract:

    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.

    View details for Web of Science ID 000079105000029

    View details for PubMedID 10092787

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