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International Immunology, Vol. 11, No. 7, 1111-1118, July 1999
© 1999 Japanese Society for Immunology

Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences

Elena Martin-Orozco, Hiroko Kobayashi, John Van Uden, Minh-Duc Nguyen, Richard S. Kornbluth and Eyal Raz

Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA

Correspondence to: E. Raz

Bacterial genomic DNA, plasmid DNA (pDNA) and synthetic oligodeoxynucleotides (ODN) containing immunostimulatory DNA sequences (ISS) have been proposed to foster a Th1 response via the release of type 1 cytokines from macrophages, dendritic cells, NK cells and B cells. In this study, we show that ISS-enriched DNA up-regulates a distinct profile of cell surface molecules on macrophages and B cells in vitro and in vivo. ISS-ODN and ISS-containing pDNA enhanced the expression of antigen presentation molecules (MHC class I and II), co-stimulatory molecules (B7-1, B7-2 and CD40), cytokine receptors (IFN-{gamma} receptor and IL-2 receptor), an adhesion molecule (ICAM-1) and an Fc receptor (Fc{gamma} receptor) on murine B cells or bone marrow-derived macrophages. The increased expression of these surface molecules is seen in purified cell populations and is largely independent of the effects of type 1 cytokines. Splenic antigen-presenting cells stimulated with ISS-ODN in vivo efficiently activate naive T cells and bias their differentiation toward a Th1 phenotype in vitro . Thus, the induction of both type 1 cytokines and a distinct profile of cell surface molecules contributes to the potent immunostimulatory effects of ISS-containing DNA on innate and adaptive immunity.

Keywords: activation markers, antigen-presenting cells, CpG motifs, immunostimulatory DNA sequences, Th1 response

The first two authors contributed equally to this work

Transmitting editor: K. Okumura


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