CD27 costimulation contributes substantially to the expansion of functional memory CD8+ T cells after peptide immunization

Taraban, V.Y., Rowley, T.F., Kerr, J.P., Willoughby, Jane E., Johnson, Peter W.M., Al-Shamkhani, A. and Buchan, S.L. (2013) CD27 costimulation contributes substantially to the expansion of functional memory CD8+ T cells after peptide immunization. European Journal of Immunology, n/a, 1-29. (doi:10.1002/eji.201343579). (PMID:24002868)

Abstract

Naive T cells require signals from multiple costimulatory receptors to acquire full effector function and differentiate to long-lived memory cells. The costimulatory receptor, CD27, is essential for optimal T-cell priming and memory differentiation in a variety of settings although whether CD27 is similarly required during memory CD8+ T-cell re-activation remains controversial. We have used OVA and anti-CD40 to establish a memory CD8+ T-cell population and report here that their secondary expansion, driven by peptide and anti-CD40, polyI:C or LPS requires CD27. Furthermore, antigenic peptide and a soluble form of the CD27 ligand, CD70 (sCD70), is sufficient for secondary memory CD8+ T-cell accumulation at multiple anatomical sites, dependent on CD80/86. Prior to boost, resting effector- and central-memory CD8+ T cells both expressed CD27 with greater expression on central memory cells. Nonetheless both populations upregulated CD27 after TCR engagement and accumulated in proportion after boosting with antigen and sCD70. Mechanistically, sCD70 increased the frequency of divided and cytolytic memory T cells, conferred resistance to apoptosis and enabled retardation of tumor growth in vivo. These data demonstrate the central role played by CD27/70 during secondary CD8+ T-cell activation to a peptide antigen, and identify sCD70 as an immunotherapeutic adjuvant for anti-tumor immunity

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Contributors

Author: Jane E. Willoughby

Author: Peter W.M. Johnson

Author: A. Al-Shamkhani

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