Role of the 2B4 Receptor in CD8+ T-Cell-Dependent Immune Control of Epstein-Barr Virus Infection in Mice With Reconstituted Human Immune System Components.
Patients with X-linked lymphoproliferative (XLP) disease due to deficiency in the adaptor molecule signaling lymphocytic activation molecule-associated protein (SAP) are highly susceptible to one specific viral pathogen, the Epstein-Barr virus (EBV). This susceptibility might result from impaired CD8(+) T-cell and natural killer cell responses to EBV infection in these patients. We demonstrate that antibody blocking of the SAP-dependent 2B4 receptor is sufficient to induce XLP-like aggravation of EBV disease in mice with reconstituted human immune system components. CD8(+) T cells require 2B4 for EBV-specific immune control, because 2B4 blockade after CD8(+) T-cell depletion did not further aggravate symptoms of EBV infection.
Viral Immunobiology, Institute of Experimental Immunology Institute of Surgical Pathology, University Hospital Zurich.
Obinna
O
Chijioke
Deparment of Experimental Medicine Center of Excellence for Biomedical Research, University of Genoa, Italy.
Emanuela
E
Marcenaro
Deparment of Experimental Medicine Center of Excellence for Biomedical Research, University of Genoa, Italy.
Alessandro
A
Moretta
Institute of Medical Virology, University of Zurich, Switzerland.
Riccarda
R
Capaul
Viral Immunobiology, Institute of Experimental Immunology.
Christian
C
Münz
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016513:Mice, SCID; D011971:Receptors, Immunologic / Q000378:metabolism*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011971:Receptors, Immunologic; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family
2B4; CD8+ T cells; EBV; HIS mice; XLP disease