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The Journal of Immunology, 1999, 163: 2999-3006.
Copyright © 1999 by The American Association of Immunologists

Differential Coupling of Second Signals for Cytotoxicity and Proliferation in CD8+ T Cell Effectors: Amplification of the Lytic Potential by B71

Matthew F. Krummel2, William R. Heath and Janette Allison

The Walter and Eliza Hall Institute, Royal Melbourne Hospital, Parkville, Australia

The role of second signals delivered through B7/CD28 interactions in T cell activation is well documented. However, once CTLs are elicited, TCR-mediated cytotoxicity appears to be uncoupled from the requirement for costimulatory signals. In this study, we show an uncoupling across a broad range of concentrations of peptide, thus demonstrating that cytolysis is a TCR-mediated response that is fully independent of costimulatory signals. However, the same T cell effectors remain fully responsive to B7 engagement, which is able to amplify Ag-mediated proliferation and cytolytic capacity. B7 expression by targets results in an IL-2-mediated proliferative expansion of the effectors concurrent with the elimination of the targets. Thus, costimulation of effectors results in a vast expansion in lytic units over time, which does not occur in the absence of IL-2 or B7. Both TCR-derived and second signals appear to be necessary to achieve this result. These results suggest that B7-expressing APC or a cohort of IL-2-producing helper cells would functionally extend the duration and effectiveness of the cytotoxic response occurring in localized immune responses.




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