Abstract
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.
Original language | English (US) |
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Pages (from-to) | 4094-4097 |
Number of pages | 4 |
Journal | Journal of Immunology |
Volume | 169 |
Issue number | 8 |
DOIs | |
State | Published - Oct 15 2002 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology