T cells demonstrate a Th1-biased response to native beta2-glycoprotein I in a murine model of anti-phospholipid antibody induction.
Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibody (AAb) to phospholipid (PL)-binding proteins, such as beta2-glycoprotein I (beta2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. beta2GPI-reactive T cells are clearly implicated in the generation of these AAb, but the mechanism responsible for their activation remains unclear. We hypothesized that immunization of mice with human beta2GPI, in the context of a potent innate immune activator lipopolysaccharide (LPS), would generate not only high titers of anti-PL AAb, but also a strong beta2GPI-specific T cell response. Healthy, nonautoimmune C57BL/6 mice were immunized repeatedly with human beta2GPI in the presence of LPS. High titers of anti-PL to beta2GPI appeared after the second immunization, with T cell reactivity to beta2GPI detectable only after the fourth immunization. Splenic T cells from these mice proliferated in response to native beta2GPI, alone or bound to anionic PL. These T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, indicating a Th1 bias of the beta2GPI-specific response. These findings suggest that T cells responsive to beta2GPI may become activated in APS patients by exposure to their cognate Ag in the context of innate immune activation and a pro-inflammatory environment.
Tolomeo
Tanya
T
Division of Rheumatology, Department of Medicine, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3G 1A4.
Rico De Souza
Angela
A
Roter
Evan
E
Dieudé
Mélanie
M
Amireault
Pascal
P
Subang
Rebecca
R
Levine
Jerrold S
JS
Rauch
Joyce
J
D000276:Adjuvants, Immunologic; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017152:Antibodies, Antiphospholipid; D008070:Lipopolysaccharides; D053482:beta 2-Glycoprotein I