Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura.
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.
Zhang
X-L
XL
Department of Haematology, Qilu Hospital, Shandong University, Jinan, China.
Peng
J
J
Sun
J-Z
JZ
Guo
C-S
CS
Yu
Y
Y
Wang
Z-G
ZG
Chu
X-X
XX
Hou
M
M
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*
D018796:Immunoconjugates; D000069594:Abatacept