title: Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus.
abstract: Effector CD8+ T cell function is impaired in systemic lupus erythematosus (SLE) and is associated with a compromised ability to fight infections. Signaling lymphocytic activation molecule family member 7 (SLAMF7) engagement has been shown to enhance natural killer cell degranulation. This study was undertaken to characterize the expression and function of SLAMF7 on CD8+ T cell subsets isolated from the peripheral blood of SLE patients and healthy subjects.
  
  
  
  CD8+ T cell subset distribution, SLAMF7 expression, and expression of cytolytic enzymes (perforin, granzyme A [GzmA], and GzmB) on cells isolated from SLE patients and healthy controls were analyzed by flow cytometry. CD107a expression and interferon-γ (IFNγ) production in response to viral antigenic stimulation in the presence or absence of an anti-SLAMF7 antibody were assessed by flow cytometry. Antiviral cytotoxic activity in response to SLAMF7 engagement was determined using a flow cytometry-based assay.
  
  
  
  The distribution of CD8+ T cell subsets was altered in the peripheral blood of SLE patients, with a decreased effector cell subpopulation. Memory CD8+ T cells from SLE patients displayed decreased amounts of SLAMF7, a surface receptor that characterizes effector CD8+ T cells. Ligation of SLAMF7 increased CD8+ T cell degranulation capacity and the percentage of IFNγ-producing cells in response to antigen challenge in SLE patients and healthy controls. Moreover, SLAMF7 engagement promoted cytotoxic lysis of target cells in response to stimulation with viral antigens.
  
  
  
  CD8+ T cell activation in response to viral antigens is defective in SLE patients. Activation of SLAMF7 through a specific monoclonal antibody restores CD8+ T cell antiviral effector function to normal levels and thus represents a potential therapeutic option in SLE.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Comte
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Karampetsou
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D052118:Lysosomal-Associated Membrane Protein 1; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; C509212:GZMA protein, human