CD70-driven costimulation induces survival or Fas-mediated apoptosis of T cells depending on antigenic load.

Abstract

Apoptosis plays an essential role in the removal of activated CD8 T cells that are no longer required during or postinfection. The Bim-dependent intrinsic pathway of apoptosis removes effector CD8 T cells upon clearance of viral infection, which is driven by withdrawal of growth factors. Binding of Fas ligand to Fas mediates activation-induced T cell death in vitro and cooperates with Bim to eliminate CD8 T cells during chronic infection in vivo, but it is less clear how this pathway of apoptosis is initiated. In this study, we show that the costimulatory TNFR CD27 provides a dual trigger that can enhance survival of CD8 T cells, but also removal of activated CD8 T cells through Fas-driven apoptosis. Using in vitro stimulation assays of murine T cells with cognate peptide, we show that CD27 increases T cell survival after stimulation with low doses of Ag, whereas CD27 induces Fas-driven T cell apoptosis after stimulation with high doses of Ag. In vivo, the impact of constitutive CD70-driven stimulation on the accumulation of memory and effector CD8 T cells is limited by Fas-driven apoptosis. Furthermore, introduction of CD70 signaling during acute infection with influenza virus induces Fas-dependent elimination of influenza-specific CD8 T cells. These findings suggest that CD27 suppresses its costimulatory effects on T cell survival through activation of Fas-driven T cell apoptosis to maintain T cell homeostasis during infection.

• Authors: Felix M Wensveen, Peter-Paul A Unger, Natasja A M Kragten, Ingrid A M Derks, Anja ten Brinke, Ramon Arens, Rene A W van Lier, Eric Eldering, Klaas P J M van Gisbergen
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 9 Pg. 4256-67 (May 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22450812 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens
• Apoptosis Regulatory Proteins
• Bcl-2-Like Protein 11
• Bcl2l11 protein, mouse
• CD27 Ligand
• Fas protein, mouse
• Membrane Proteins
• Peptides
• Proto-Oncogene Proteins
• Tumor Necrosis Factor Receptor Superfamily, Member 7
• fas Receptor

Topics

• Animals
• Antigens (genetics, immunology, metabolism)
• Apoptosis (genetics, immunology)
• Apoptosis Regulatory Proteins (genetics, immunology, metabolism)
• Bcl-2-Like Protein 11
• CD27 Ligand (genetics, immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cell Survival (genetics, immunology)
• Chronic Disease
• Immunologic Memory (genetics)
• Infections (genetics, immunology, metabolism)
• Membrane Proteins (genetics, immunology, metabolism)
• Mice
• Mice, Knockout
• Peptides (genetics, immunology, metabolism)
• Proto-Oncogene Proteins (genetics, immunology, metabolism)
• Signal Transduction
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (genetics, immunology, metabolism)
• fas Receptor (genetics, immunology, metabolism)