Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 51, Pages 19454-19459Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0609706104
Keywords
CD70; granzyme B; interferon-gamma; TNF receptor superfamily
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Funding
- Wellcome Trust Funding Source: Medline
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The clonal expansion of antigen-specific CD8(+) T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8(+) T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor a. This pathway for clonal expansion of the CD8(+) T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8(+) T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8(+) T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8(+) T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8(+) T cells in persistent viral infections.
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