Modulation of immune response with CTLA4-Ig-induced anergic T cells in chronic idiopathic thrombocytopenic purpura.
Journal of thrombosis and haemostasis : JTH 2007 Oct 17; 6(1):158-65
Zhang X XL, Peng J J, Sun J JZ, Guo C CS, Yu Y Y, Wang Z ZG, Chu X XX, Hou M M
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Background: Platelet glycoprotein (GP)-reactive CD4(+) T cells are essential to the stimulation and maintenance of antiplatelet autoantibody production in chronic idiopathic thrombocytopenic purpura (ITP). Blocking costimulatory signals could result in platelet-specific T cell anergy. Methods: GP-specific CD4(+) T cells from patients with ITP were induced anergic using CTLA4-Ig. The CTLA4-Ig-induced GP-specific anergic T cells were detected for their inhibitory function on GP-reactive T cell proliferation and antibody production by performing in vitro culture systems. To further analyzed their tolerizing mechanisms, we cocultured GP-anergic T cells with dendritic cells (DCs) from patients with ITP. Results: Our studies demonstrated that the anergized GP-specific T cells have profound effects on both GP-specific T cell proliferation and antibody production. These anergic T cells exerted their suppressive effects mainly in a cell-contact-dependent manner, and they were not constitutively suppressive but required specific antigen stimulation to make DCs tolerogenic. The anergic T cell-modulated DCs could induce the autoreactive T cells tolerant, which was not restricted to T cells of the same specificity. Conclusion: Our studies demonstrate the efficacy of CTLA4-Ig in suppressing the pathologic autoimmune responses in ITP. These findings provide new insights into the underlying mechanisms of anergy induction in chronic ITP.
Keywords: idiopathic thrombocytopenic purpura