The Costimulatory Molecule CD27 Maintains Clonally Diverse CD8 + T Cell Responses of Low Antigen Affinity to Protect against Viral Variants

• Published in: Immunity (Cambridge, Mass.) Vol. 35; no. 1; pp. 97 - 108
• Main Authors: van Gisbergen, Klaas P.J.M., Klarenbeek, Paul L., Kragten, Natasja A.M., Unger, Peter-Paul A., Nieuwenhuis, Marieke B.B., Wensveen, Felix M., ten Brinke, Anja, Tak, Paul P., Eldering, Eric, Nolte, Martijn A., van Lier, Rene A.W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-07-2011; Elsevier Limited
• Subjects: Animals; Antigenic Variation; Antigens; Antigens, Viral - immunology; Apoptosis; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell division; Clone Cells; Cloning; Humans; Immune system; Immunologic Memory; Influenza A virus - immunology; Influenza A virus - pathogenicity; Lymphocyte Activation - genetics; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Orthomyxoviridae Infections - immunology; Peptides; Spleen; Statistical analysis; T cell receptors; T-Cell Antigen Receptor Specificity - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2011.04.020

CD70 and CD27 are costimulatory molecules that provide essential signals for the expansion and differentiation of CD8
+ T cells. Here, we show that CD27-driven costimulation lowered the threshold of T cell receptor activation on CD8
+ T cells and enabled responses against low-affinity antigens. Using influenza infection to study in vivo consequences, we found that CD27-driven costimulation promoted a CD8
+ T cell response of overall low affinity. These qualitative effects of CD27 on T cell responses were maintained into the memory phase. On a clonal level, CD27-driven costimulation established a higher degree of variety in memory CD8
+ T cells. The benefit became apparent when mice were reinfected, given that CD27 improved CD8
+ T cell responses against reinfection with viral variants, but not with identical virus. We propose that CD27-driven costimulation is a strategy to generate memory clones that have potential reactivity to a wide array of mutable pathogens.
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► CD70 and CD27 enable proliferation and survival of low-affinity CD8
+ T cells ► CD27 maintains effector and memory CD8
+ T cells of low affinity in vivo ► CD27 establishes enhanced clonal diversity in the memory CD8
+ T cell pool ► CD27 enhances recall responses against variant, but not identical, viral epitopes