title: Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura.
abstract: BACKGROUND
  Platelet glycoprotein (GP)-reactive CD4+ T cells are essential for 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 made anergic using cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig). The CTLA4-Ig-induced GP-specific anergic T cells were investigated for their inhibitory function on GP-reactive T-cell proliferation and antibody production with in vitro culture systems. To further analyze 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 to be tolerant, and this effect was not restricted to T cells of the same specificity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Sun
authors.forename: C-S
authors.initials: CS
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Wang
authors.forename: X-X
authors.initials: XX
authors.lastname: Chu
authors.forename: M
authors.initials: M
authors.lastname: Hou
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000187:drug effects; D017951:Antigen Presentation; D015551:Autoimmunity / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D018796:Immunoconjugates / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*
chemical_list: D018796:Immunoconjugates; D000069594:Abatacept