Functional analysis of auto-reactive T cell clones in idiopathic thrombacytopenic purpura
Project/Area Number |
18591069
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Ehime University |
Principal Investigator |
HATO Takaaki Ehime University, University Hospital, Associate Professor (30172943)
|
Co-Investigator(Kenkyū-buntansha) |
YASUKAWA Masaki Ehime University, Graduate School of Medicine, Professor (60127917)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | platelet / idiopathic thrombocytopenic immure / mteerin / GPTTh-Tira / talin / T細胞 |
Research Abstract |
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.
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Report
(3 results)
Research Products
(48 results)
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[Journal Article] Cooperative role of the membrane-proximal and distal residues of the integrin ?3 cytoplasmic domain in regulation of talin-mediated fib? 3 activation2008
Author(s)
Hato, T, Yamanouchi, J, Tamura, T, Yakushijin, Y, Sakai, I, Yasukawa, M
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Journal Title
Journal of Biological Chemistry 283
Pages: 5662-5668
Description
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[Journal Article] Absence of chlamydial infection in Japanese patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue2007
Author(s)
Yakushijin, Y, Kodama, T, Takaoka, I, Tanimoto, K, Bessho, H, Sakai, I, Hato, T, Hasegawa, H, Yasukawa, M
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Journal Title
International Journal of Hematology 85
Pages: 223-230
NAID
Description
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[Journal Article] Follicular dendritic cell tumor as unknown primary tumor2007
Author(s)
Yakushijin, Y, Shikata, H, Kito, K, Ohshima, K, Kojima, K, Hato, T, Hasegawa, H, Yasukawa, M
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Journal Title
International Journal of Clinical Oncology 12
Pages: 56-58
NAID
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[Journal Article] Budd-Chiari syndrome associated with hypereosinophilic syndrome ; A case report2007
Author(s)
Inoue, A, Michitaka, K, Shigematsu, S, Konishi, I, Hirooka, M, Hiasa, Y, Matsui, H, Matsuura, B, Horiike, N, Hato, T, Miyaoka, H, Onji, M
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Journal Title
Internal Medicine 46
Pages: 1095-1100
NAID
Description
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[Journal Article] Human herpesvirus 6 impairs differentiation of monocytes to dendritic cells2006
Author(s)
Niiya, H, Lei, J, Guo, Y, Azuma, T, Yakushijin, Y, Sakai, I, Hato, T, Tohyama, M, Hashimoto, K, Yasukawa, M
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Journal Title
Experimental Hematology 34
Pages: 642-653
Description
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[Journal Article] Cappucino mutation in an autoimmune-prone strain of mice suggests a role of platelet function in the progression of immune complex crescentic elomerulonenhritis2006
Author(s)
Yoshida, M, Saiga, K, Hato, T, Iwaki, S, Niiya, T, Arita, N, Komori, H, Tsubaki, T, Furukawa, H, Terada, M, Maeyama, K, Nemoto, K, Nose, M, Ono, M
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Journal Title
Arthritis and Rheumatism 54
Pages: 2934-2943
Description
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