title: Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura.
abstract: Chronic autoimmune thrombocytopenic purpura (AITP) is characterized by platelet-specific autoantibody production that is influenced by enhanced antiplatelet 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 cytologic T-lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig), and cyclosporin A (CsA), alone or in combination, on induction of platelet-specific T-cell anergy. The data showed that in most cases CTLA4-Ig and/or CsA could induce tolerance toward 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 interleukin 2 (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. CTLA4-Ig may become a promising new therapeutic agent for the treatment of chronic AITP, and the combination of CTLA4-Ig and CsA would be a more powerful strategy for the management of refractory AITP.
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China. junpeng88@sina.com.cn
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Chuanfang
authors.initials: C
authors.lastname: Liu
authors.forename: Dai
authors.initials: D
authors.lastname: Liu
authors.forename: Cuiai
authors.initials: C
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Wang
authors.forename: Nianzeng
authors.initials: N
authors.lastname: Xing
authors.forename: Conggao
authors.initials: C
authors.lastname: Xu
authors.forename: Xueliang
authors.initials: X
authors.lastname: Chen
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ji
authors.forename: Maohong
authors.initials: M
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D016824:Antigens, Human Platelet / Q000276:immunology*; D018122:B7-1 Antigen / Q000187:drug effects; D001792:Blood Platelets / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D017635:Clonal Anergy / Q000187:drug effects* / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016824:Antigens, Human Platelet; D018122:B7-1 Antigen; D018796:Immunoconjugates; D000069594:Abatacept; D016572:Cyclosporine