Research Project
Grant-in-Aid for Scientific Research (C)
To explore the interaction between dendritic cells/T cells and the platelet membrane protein, GPIIb-IIIa, we established T cell clones recognizing the GPIIb amino acid sequences from patients with idiopathic thrombocytopenic purpura (ITP). These clones were composed of CD4+ helper T cells and CD8+ cytotoxic T cells. The HP patients with CD8+ T cell clones showed lower number of megakaryocytes in bone marrow, as compared with patients with CD4+ helper T cell clones. This finding suggests that CD8+ cytotoxic T cells destruct autologous platelets in some ITP patients. Platelet destruction in ITP has been believed to be mediated by autoantibody. Our results suggest T cell-mediated cytotoxicity is an alternative mechanism for platelet destruction in a subset of ITP and that different autoimmune-mediated mechanisms are involved in pathogenesis of ITP.We also examined structure and function of the GPIIb-IIIa molecule by using an expression system for mutated recombinant GPIIb -Ma on the surface of mammalian cells. We identified amino acids critical for regulation of GPIIb-IIIa activation in a certain loop of extracellular domain of GPIIIa. Moreover, we found two amino acids critical for regulation of GPIIb-IIIa activation in the cytoplasmic domain of GPIIIa and that these two residues cooperatively regulate talin-mediated GPIIb-IIIa activation.
All 2008 2007 2006
All Journal Article (18 results) (of which Peer Reviewed: 8 results) Presentation (30 results)
Journal of Biological Chemistry 283
Pages: 5662-5668
International Journal of Hematology 85
Pages: 223-230
International Journal of Clinical Oncology 12
Pages: 56-58
Internal Medicine 46
Pages: 1095-1100
10019488927
10018565811
130000076129
Experimental Hematology 34
Pages: 642-653
Journal of Thrombosis and Haemostasis 4
Pages: 2278-2280
Arthritis and Rheumatism 54
Pages: 2934-2943
Exp Hematol 34・5
J Thromb Hemost 4・
Arthritis Rheum 54・9
