title: Lupus-prone mice fail to raise antigen-specific T cell responses to intracellular infection.
abstract: Systemic lupus erythematosus (SLE) is characterized by multiple cellular abnormalities culminating in the production of autoantibodies and immune complexes, resulting in tissue inflammation and organ damage. Besides active disease, the main cause of morbidity and mortality in SLE patients is infections, including those from opportunistic pathogens. To understand the failure of the immune system to fend off infections in systemic autoimmunity, we infected the lupus-prone murine strains B6.lpr and BXSB with the intracellular parasite Toxoplasma gondii and survival was monitored. Furthermore, mice were sacrificed days post infection and parasite burden and cellular immune responses such as cytokine production and cell activation were assessed. Mice from both strains succumbed to infection acutely and we observed greater susceptibility to infection in older mice. Increased parasite burden and a defective antigen-specific IFN-gamma response were observed in the lupus-prone mice. Furthermore, T cell:dendritic cell co-cultures established the presence of an intrinsic T cell defect responsible for the decreased antigen-specific response. An antigen-specific defect in IFN- gamma production prevents lupus-prone mice from clearing infection effectively. This study reveals the first cellular insight into the origin of increased susceptibility to infections in SLE disease and may guide therapeutic approaches.
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Lieberman
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D042541:Intracellular Space / Q000469:parasitology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology* / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan