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J. Virol. doi:10.1128/JVI.00919-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CD40 engagement on dendritic cells, but not on B or T cells, is required for the long-term control of murine gammaherpesvirus-68 (MHV-68)

Viral Immunology, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121

^* To whom correspondence should be addressed. Email: ssarawar{at}tpims.org.

	Abstract

CD4 T cells are not essential for primary clearance of replicating murine gammaherpesvirus 68 (MHV-68) but are required for effective long-term control. The virus reactivates in the lungs of MHC Class II deficient (CII-/-) mice that lack functional CD4 T cells. CD40L is upregulated on activated CD4 T cells and it is thought that CD40-CD40L interactions are an important component of CD4 T cell help. Our previous studies have shown that agonistic antibodies to CD40 can substitute for CD4 T cell function in the long-term control of MHV-68. In the present study, we sought to identify the CD40-positive cell type mediating this effect. To address this question, we adoptively-transferred MHV-68 peptide-pulsed CII-/- dendritic cells (DC) that had been treated with an agonistic antibody to CD40, to MHV-68-infected CII-/- recipients. Viral reactivation was significantly lower in mice injected with anti-CD40-treated DC than in those injected with control DC, or in mice that did not receive any DC. However, in similar experiments with B cells, anti-CD40 treatment had no effect. We also investigated the requirement for CD40 expression on T cells by adoptive transfer of T cells from CD40+/+ or -/- mice into T cell-deficient recipients that were subsequently infected with MHV-68. The results showed that CD40 expression on T cells is not necessary for preventing viral reactivation. Taken together, our data suggest that CD40 engagement on DC, but not on T or B cells, is essential for effective long-term control of MHV-68.

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