Journal of thrombosis and haemostasis : JTH · 2007
Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura.
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Zhang X-L, Peng J, Sun J-Z, Guo C-S, Yu Y, Wang Z-G, Chu X-X, Hou M
Аннотация
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.
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.