T cells demonstrate a Th1-biased response to native β2-glycoprotein I in a murine model of anti-phospholipid antibody induction

Abstract

Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibody (AAb) to phospholipid (PL)-binding proteins, such as β2-glycoprotein I (β2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. β2GPI-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 β2GPI, 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 β2GPI-specific T cell response. Healthy, nonautoimmune C57BL/6 mice were immunized repeatedly with human β2GPI in the presence of LPS. High titers of anti-PL to β2GPI appeared after the second immunization, with T cell reactivity to β2GPI detectable only after the fourth immunization. Splenic T cells from these mice proliferated in response to native β2GPI, alone or bound to anionic PL. These T cells produced IL-2 and IFN-γ, but not IL-4 or IL-10, indicating a Th1 bias of the β2GPI-specific response. These findings suggest that T cells responsive to β2GPI may become activated in APS patients by exposure to their cognate Ag in the context of innate immune activation and a pro-inflammatory environment.

• β2-Glycoprotein I
• TC
• anti-phospholipid syndrome
• systemic lupus erythematosus (SLE)
• rodent
• autoimmunity