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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-06-1666.
Submitted June 6, 2002
Accepted November 10, 2002
Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura
Jun Peng*, Chuanfang Liu, Dai Liu, Cuiai Ren, Wei Li, Zhenguang Wang, Nianzeng Xing, Conggao Xu, Xueliang Chen, Chunyan Ji, Maohong Zhang, and Ming Hou
Department of Hematology, Qilu Hospital of Shandong University, Jinan, China
Department of Nuclear Medicine, Qilu Hospital of Shandong University, Jinan, China
Department of Hematology, Weifang People's Hospital, Weifang, China
Department of Hematology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, China
Department of Science and Technology, Shandong University, Jinan, China
Department of Urology, Beijing Chao Yang Hospital affiliated to Capital University of Medical Sciences, Beijing, China
* Corresponding author; email: junpeng88{at}sina.com.cn.
Chronic autoimmune thrombocytopenic purpura (AITP) is characterized by platelet-specific autoantibody production which is influenced by enhanced anti-platelet T helper cell reactivity. Costimulatory signals are absolutely required for T cell activation and play key roles in the decision between tolerance and immunity. In this study we cultured T cells isolated from patients with chronic AITP to investigate the effects of the B7-blocking agent CTLA-4Ig, and CsA, alone or in combination, on induction of platelet-specific T cell anergy. The data showed that in most cases CTLA-4Ig and/or CsA could induce tolerance towards platelet antigens based on anergy. It could be overcome by stimulation with unrelated antigens demonstrating its platelet specificity. The anergy is associated with lack of IL-2 and withheld by exogenous IL-2, emphasizing the pivotal role of IL-2 suppression in the induction of platelet-specific anergy. We also prospectively evaluated the efficacy of CsA therapy in patients with refractory AITP and observed that the response to CsA treatment in vivo was associated with the inhibiting sensitivity of platelet-reactive T cells to CsA in vitro. This suggests that the sensitivity of T cells to CsA in vitro could serve as a reliable parameter in predicting the efficacy of CsA for patients with refractory AITP. CTLA-4Ig may become a promising new therapeutic agent for the treatment of chronic AITP and the combination of CTLA-4Ig and CsA would be a more powerful strategy for the management of refractory AITP.
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