Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody

• Published in: The Journal of clinical investigation Vol. 102; no. 7; pp. 1393 - 1402
• Main Authors: Kuwana, M, Kaburaki, J, Ikeda, Y
• Format: Journal Article
• Language: English
• Published: United States 01.10.1998
• Subjects: Adult; Aged; Antigens, CD - immunology; Autoantibodies - blood; Blood Platelets - immunology; Cells, Cultured; Female; Humans; Kinetics; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation; Male; Middle Aged; Platelet Glycoprotein GPIIb-IIIa Complex - immunology; Purpura, Thrombocytopenic, Idiopathic - blood; Purpura, Thrombocytopenic, Idiopathic - immunology; Reference Values; T-Lymphocytes - immunology
• ISSN: 0021-9738
• DOI: 10.1172/JCI4238

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.