Differential coupling of second signals for cytotoxicity and proliferation in CD8(+) T cell effecters: Amplification of the lytic potential by B7
- Author(s)
- Krummel, MF; Heath, WR; Allison, J;
- Details
- Publication Year 1999-09-15,Volume 163,Issue #6,Page 2999-3006
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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 effecters 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 effecters concurrent with the elimination of the targets. Thus, costimulation of effecters 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- NATURAL-KILLER-CELLS; CD28 COSTIMULATION; TUMOR REJECTION; MEDIATED CYTOTOXICITY; LYMPHOCYTES-T; IN-VITRO; ACTIVATION; RECEPTOR; INTERLEUKIN-2; EXPRESSION
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- Refer to copyright notice on published article.
Creation Date: 1999-09-15 12:00:00