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The Journal of Immunology, 2002, 168: 4907-4913.
Copyright © 2002 by The American Association of Immunologists

IFN-{alpha}{beta} Promote Priming of Antigen-Specific CD8+ and CD4+ T Lymphocytes by Immunostimulatory DNA-Based Vaccines1

Hearn Jay Cho2,*, Tomoko Hayashi{dagger}, Sandip K. Datta{dagger}, Kenji Takabayashi{dagger}, John Henry Van Uden{dagger}, Anthony Horner{dagger}, Maripat Corr{dagger} and Eyal Raz{dagger}

* Division of Hematology/Medical Oncology, Department of Medicine, New York Presbyterian Hospital and Cornell Medical Center, and Laboratory of Neuro-Oncology, Rockefeller University, New York, NY 10021; and {dagger} Department of Internal Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California at San Diego, La Jolla, CA 92093

Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides stimulate NK and APC to secrete proinflammatory cytokines, including IFN-{alpha}{beta} and -{gamma}, TNF-{alpha}, and IL-6 and -12, and to express costimulatory surface molecules such as CD40, B7-1, and B7-2. Although ISS DNA has little direct effect on T cells by these criteria, immunization of wild-type mice with ISS DNA and OVA results in Ag-specific CTL and Th1-type T helper activity. This investigation examines the mechanisms by which ISS DNA primes CD8+ and CD4+ lymphocyte activities. In this report we demonstrate that ISS DNA regulates the expression of costimulatory molecules and TAP via a novel autocrine or paracrine IFN-{alpha}{beta} pathway. Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8+ CTL, whereas CD40, B7, and IL-12 costimulation is required for priming of CD4+ Th cells by ISS-based vaccines.




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