Genetic analysis of the 4C8 antigen on T cells which stimultes production of TNF-a by synoviocytes from patients with rheumatoid arthritis.
| Project/Area Number |
09670488
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MASUYAMA Jun-ichi Jichi Medical School, Division of Rheumatology and Clinical Immunology, Assistant Professor, 医学部・アレルギー膠原病科, 講師 (20165731)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Rheumatoid Arthritis / TNF-a / T cell / Synoviocyte / transmigration / T細胞膜抗原 |
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| Research Abstract |
We developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26 expressing (CD26^<hi>) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. This mAb also appears to inhibit TNF-alphat production by the interaction between T cells and synoviocytes from patients with rheumatoid arthritis. Anti-4C8 reacted with all CD3+ T cells and monocytes, but not neutrophils or HUVECs. The structure defined by this antibody was an 80 kDa molecule. The mAb at 1 mug/ml inhibited 80-90% of migration of CD3+ T cells through unstimulated and IFN-gamma-stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase-contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVE
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Cs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 mug/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26^<hi>. Second, solid-phase immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26^<hi> T cells when added to T cells at a high dose of 10 gg/ml. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26^<hi> cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26^<hi> cells adherent to HUVEC.The cloning of the gene coding this antigen is proceeding now. Less
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Report
(3 results)
Research Products
(21 results)
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[Publications] Nakamura M,Furukawa Y,Sasaki R,Masuyama Ji, Kikuchi J,Iwase S,Kudo T,Narimatsu H,Asakura S,Fujiwara S,Inokuchi Ji: "UDP-GlcNAc : Galbetal-->3GalNAc (GlcNAc to GalNAc) betal-->6N-acetylglucosaminyltransferase holds a key role onthe control of CD15s expression in human pre-B lymphoid cell lines." Glycobiology. 9. 1-12 (1999)
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「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Funayama H,Ikeda U,Takahashi M,Sakata Y,Kitagawa S,Takahashi Y,Masuyama J,Furukawa Y,Miura Y,Kano S,Matsuda M,Shimada K: "Human monocyte-endothelial cell interaction induces platelet-derived growth factor expression." Cardiovasc Res. 37. 216-224 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
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