A Crucial Role for B7-CD28 in Transmitting T Help from APC to CTL

• Published in: The Journal of immunology (1950) Vol. 169; no. 8; pp. 4094 - 4097
• Main Authors: Prilliman, K R, Lemmens, EE, Palioungas, G, Wolfe, T G, Allison, J P, Sharpe, AH, Schoenberger, S P
• Format: Journal Article
• Language: English
• Published: 15.10.2002
• ISSN: 0022-1767

Although APC activation via CD40-CD40L signaling plays a critical role in enabling CD4 super(+) 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 super(+) 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.