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The Cross-Priming APC Requires a Rel-Dependent Signal to Induce CTL¹

Justine D. Mintern^*,, Gabrielle Belz^*, Steve Gerondakis^*, Francis R. Carbone^2, and William R. Heath^2,*,

^* Immunology Division, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia; and Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Australia

Induction of OVA-specific CTL by cross-priming requires help from CD4 T cells, which use CD154 to signal CD40 on the APC. To further dissect the molecular pathways involved in cross-priming, we examined the role of Rel, an NF-B family member. c-rel^-/- mice failed to generate OVA-specific CTL by cross-priming, but could induce CTL to HSV-1. Using chimeric mice, Rel expression was shown to be required by the APC, but not by the T cells. Notably, the deficiency in Rel could be overcome by triggering CD40, implying that the APC required Rel before receipt of the CD40 signal. These data suggest that the cross-priming APC must receive two signals before it can stimulate CTL. The first signal is Rel dependent and is required before activation of CD4 helper T cells, which then deliver the second signal using CD154 to trigger CD40.

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