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Modulation of immune response with cytotoxic T‐lymphocyte‐associated antigen 4 immunoglobulin‐induced anergic T cells in chronic idiopathic thrombocytopenic purpura 2
Author(s) -
ZHANG X.L.,
PENG J.,
SUN J.Z.,
GUO C.S.,
YU Y.,
WANG Z.G.,
CHU X.X.,
HOU M.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02804.x
Subject(s) - cytotoxic t cell , immunology , antigen , t cell , clonal anergy , immune system , antibody , immune tolerance , medicine , biology , in vitro , t cell receptor , biochemistry
Summary. 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. 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.