Elimination of chronic viral infection by blocking CD27 signaling

Matthias Matter; Bernhard Odermatt; Hideo Yagita; Jean-Marc Nuoffer; Adrian F Ochsenbein

doi:10.1084/jem.20060651

Elimination of chronic viral infection by blocking CD27 signaling

J Exp Med. 2006 Sep 4;203(9):2145-55. doi: 10.1084/jem.20060651. Epub 2006 Aug 21.

Authors

Matthias Matter¹, Bernhard Odermatt, Hideo Yagita, Jean-Marc Nuoffer, Adrian F Ochsenbein

Affiliation

¹ Tumor Immunology, Department of Clinical Research, Institute of Clinical Chemistry, Inselspital, University of Berne, and Department of Pathology, University Hospital, Zurich, Switzerland.

Abstract

Neutralizing antibody (nAb) responses to lymphocytic choriomeningitis virus (LCMV) in mice and immunodeficiency virus and hepatitis C virus in humans are usually weak and slow to develop. This may be the result of structural properties of the surface glycoprotein, a low frequency of B cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nAbs. In this study, we show that during LCMV infection, CD27 signaling on CD4+ T cells enhances the secretion of interferon-gamma and tumor necrosis factor-alpha. These inflammatory cytokines lead to the destruction of splenic architecture and immunodeficiency with reduced and delayed virus-specific nAb responses. Consequently, infection with the otherwise persistent LCMV strain Docile was eliminated after CD27 signaling was blocked. Our data provide a novel mechanism by which LCMV avoids nAb responses and suggest that blocking the CD27-CD70 interaction may be an attractive strategy to prevent chronic viral infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Antibodies, Viral / biosynthesis
Antibodies, Viral / immunology
Antigens, CD / immunology
CD27 Ligand
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
Chronic Disease
Humans
Immunosuppression Therapy
Interferon-gamma / immunology
Lymphocytic Choriomeningitis / immunology*
Lymphocytic Choriomeningitis / virology
Lymphocytic choriomeningitis virus / immunology*
Membrane Proteins / immunology
Mice
Mice, Knockout
Neutralization Tests
Signal Transduction*
Spleen / cytology
Spleen / immunology
Spleen / pathology
Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*
Tumor Necrosis Factor-alpha / immunology
Tumor Necrosis Factors / immunology

Substances

Antibodies, Viral
Antigens, CD
CD27 Ligand
CD70 protein, human
Cd70 protein, mouse
Membrane Proteins
Tumor Necrosis Factor Receptor Superfamily, Member 7
Tumor Necrosis Factor-alpha
Tumor Necrosis Factors
Interferon-gamma