Submitted July 19, 2002
Accepted December 31, 1969
Suppression of autoreactive T-cell response to glycoprotein IIb-IIIa by blockade of CD40/CD154 interaction: implications for treatment of immune thrombocytopenic purpura
Masataka Kuwana*, Yutaka Kawakami, and Yasuo Ikeda
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
* Corresponding author; email: kuwanam{at}sc.itc.keio.ac.jp.
The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb-IIIa (GPIIb-IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb-IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb-IIIa. Repeated antigenic stimulation of GPIIb-IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb-IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low IFN-
and high IL-10, and suppressed anti-GPIIb-IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function, and could be a therapeutic option for suppressing pathogenic autoimmune responses in ITP patients.
