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Cutting Edge |
* Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
Howard Hughes Research Institute, Division of Immunology, Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720;
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
Although APC activation via CD40-CD40L signaling plays a critical role in enabling CD4+ T cells to provide the "help" necessary for cross-priming of naive CTL, it is unclear how this makes the APC competent for priming. We have investigated the roles of B7-1/B7-2 and their TCRs CD28/CTLA-4 in cross-priming of CD4-dependent CTL in vivo. We find that both CD28 and B7-1/B7-2 are required for CD40-activated APC to cross-prime CTL, and that priming by CD40-activated APC was prevented by blockade of CD28. Conversely, augmenting CD28 signals with an agonistic Ab bypassed the requirement for CD4+ T help or CD40 activation. Interestingly, blockade of the negative regulatory B7 receptor CTLA-4 failed to prime CTL in the absence of T help. These results support a model in which activation-induced up-regulation of B7 molecules on APC leads to increased CD28 signaling and a commitment to cross-priming of CD4-dependent CTL.
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