Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.
T cell proliferative responses to platelet membrane GPIIb-IIIa were examined in 14 patients with chronic immune thrombocytopenic purpura (ITP), 7 systemic lupus erythematosus (SLE) patients with or without thrombocytopenia, and 10 healthy donors. Although peripheral blood T cells from all subjects failed to respond to the protein complex in its native state, reduced GPIIb-IIIa stimulated T cells from three ITP patients and one SLE patient with thrombocytopenia, and tryptic peptides of GPIIb-IIIa stimulated T cells from nearly all subjects. The specificity of the responses for GPIIb-IIIa was confirmed by activation of GPIIb-IIIa-primed T cells by a recombinant GPIIbalpha fragment in secondary cultures. Characterization of T cell response induced by modified GPIIb-IIIa showed that the response was restricted by HLA-DR, the responding T cells had a CD4(+) phenotype, and the proliferation was accelerated only in ITP patients, suggesting in vivo activation of these T cells. In vitro IgG anti-GPIIb-IIIa synthesis in PBMC cultures was induced by modified GPIIb-IIIa specifically in ITP patients with platelet-associated anti-GPIIb-IIIa antibody. Anti-GPIIb-IIIa antibody produced in supernatants was absorbed by incubation with normal platelets. In summary, CD4(+) and HLA-DR-restricted T cells to GPIIb-IIIa are involved in production of anti-platelet autoantibody in ITP patients and are related to the pathogenic process in chronic ITP.
Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. kuwanam@med.keio.ac.jp
M
M
Kuwana
J
J
Kaburaki
Y
Y
Ikeda
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D001323:Autoantibodies; D019039:Platelet Glycoprotein GPIIb-IIIa Complex