Emergence of polyclonal autoantibody responses to multiple platelet surface glycoproteins in regulatory T cell-deficient mice. (115.28)

Abstract

Abstract Naturally occurring CD4+CD25+Foxp3+ regulatory T cells (Tregs) are known to play an important role in preventing pathogenic autoimmune responses. Recently, we have found that approximately one third of mice deficient of CD4+CD25+Foxp3+ Tregs spontaneously develop thrombocytopenia with increased platelet-associated IgG, analogous to patients with immune thrombocytopenia. To identify platelet autoantigens in Treg-deficient mice, plasma samples from thrombocytopenic and non-thrombocytopenic Treg-deficient mice were subjected to immunoblots using platelets as an antigen in reduced and non-reduced conditions. IgG antibodies to platelet surface glycoproteins, such as GPIb, GPIIb, and GPIIIa, were detected specifically in thrombocytopenic mice in various combinations. IgG antibodies to native platelets were further assessed by flow cytometry using platelet eluates and splenocyte culture supernatants. IgG antibodies capable of binding to native platelets were detected in thrombocytopenic, but not in non-thrombocytopenic mice. Antibody reactivity was cancelled in the majority of samples when platelets derived from GPIb-deficient or GPIIIa-deficient mice were used instead of wild-type platelets as an antigen. In summary, Treg deficiency alone leads to emergence of polyclonal IgG autoantibody responses to native and denatured platelet surface glycoproteins, supporting a critical role of CD4+CD25+Foxp3+ Tregs in suppressing induction of autoimmunity.