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CD27 is required for generation and long-term maintenance of T cell immunity

Abstract

The Traf-linked tumor necrosis factor receptor family member CD27 is known as a T cell costimulatory molecule. We generated CD27−/− mice and found that CD27 makes essential contributions to mature CD4+ and CD8+ T cell function: CD27 supported antigen-specific expansion (but not effector cell maturation) of naïve T cells, independent of the cell cycle–promoting activities of CD28 and interleukin 2. Primary CD4+ and CD8+ T cell responses to influenza virus were impaired in CD27−/− mice. Effects of deleting the gene encoding CD27 were most profound on T cell memory, reflected by delayed response kinetics and reduction of CD8+ virus-specific T cell numbers to the level seen in the primary response. This demonstrates the requirement for a costimulatory receptor in the generation of T cell memory.

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Acknowledgements

We thank E. Tanger, M. Timpico, L. Tolkamp, T. Schrauwers, H. Starrevelt and other staff of the Animal Facility of the Netherlands Cancer Institute for biotechnical assistance and maintenance of the mice; A. A. M. Hart for expert statistical analysis; G. Rimmelzwaan for virus preparations and advice; E. Noteboom and A. Pfauth for assistance with flow cytometry; P. Krimpenfort, J. Haanen, G. Dingjan, R. Hendriks and J. Kirberg for experimental advise and assistance; and A. M. Kruisbeek for reading the manuscript. Supported by The Netherlands Organization for Scientific Research (NWO).

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Correspondence to Jannie Borst.

Supplementary information

Web Figure 1

CD27 does not contribute to cytolytic effector cell maturation. Cytotoxicity of spleen cells from infected mice. Spleen cells collected from CD27 +/+ (closed squares) and CD27-/- (open squares) mice infection were cultured for 7 days with NP(366-374) peptide and IL-2. Next, cells were tested for specific cytotoxicity towards EL-4 thymoma cells, loaded with NP(366-374) peptide in a standard 5-h 51Cr-release assay at the indicated effector (E) to target (T) cell ratios. Activity on EL-4 targets without peptide was negligible. Values represent means and standard deviations of triplicate samples in one experiment. The experiment is representative of three. Spleen cells were collected from mice at day 14 after primary infection (upper panel) or at day 11 after secondary infection (lower panel).

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Figure 1: Tnfrsf7-targeting strategy and result.
Figure 2: CD27 does not affect T cell division.
Figure 3: CD27 is important for generation of T cell immunity to influenza virus.
Figure 4: CD27 is required for T cell memory.
Figure 5: CD27 contributes to the antigen-specific CD4+ T cell response.