CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation

Carr, J. M., Carrasco, M. J., Thaventhiran, J. E. D., Bambrough, P. J., Kraman, M., Edwards, A. D. ORCID: https://orcid.org/0000-0003-2369-989X, Al-Shamkhani, A. and Fearon, D. T. (2006) CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation. Proceedings of the National Academy of Sciences, 103 (51). p. 19454. ISSN 0027-8424 doi: 10.1073/pnas.0609706104

Abstract/Summary

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 alpha. 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.