| Co-Investigator(Kenkyū-buntansha) |
NISHIZUKA Yasuaki Aichi Canoer Center Research Institute (Higuchi,Masa), 所長 (60073095)
MORISHITA Reiji Faculty of Medicine, Kyoto University, 医学部, 助教授 (60027464)
KURIBAYASHI Kagemasa Faculty of Medicine, Kyoto University, 医学部, 助手 (10064578)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1987: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1986: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Research Abstract |
Experimental autoimmune gastritis (AIG), defined by the appearance of autoantibodies to parietal cells, was induced by neonatal thymectomy in BALB/c mice three days after birth. Clinical findings, such as decrease in Vitamin B_<12> absorption and intrinsic factor, indicate similarity to humal pernicious anemia. Immunologically, AIG mice exhibited delayed type hypersensitivity(DTH) reaction to parietal cells; suggesting that DTH is involved in the mechanism of tissue damage. In fact, cytofluorometric and immunohistochemical analysis revealed T cell infiltration at an early stage (1-3 mo. after thymectomy). However, B cells also infiltrate at a late stage; implying that B cells themselves in addition to autoantibodies produced by B cells, are involved in the development of the disease. Thus, autoantigens recognized by T and B cedlls must play an important fole for induction of the disease. To analyze the autoantigens of parietal cells, hybridomas producing monoclonal autoantibodies to parietal cells were establishedfrom an AIG mouse bearing circulating autoantibody to parietal cells. Among three clones thus obtained, two (2B6 and 2G10) reacted with protein while one (1H9) with perhaps carbohydrate when assayed by ELISA using Triton-X100 solubilized gastric extracts. 2G10 recognized species-specific, while 2B6 and 1H9 interspecies-specific antigenic determinants. Molecular weight of this molecules is approximately 600KD, consisting of 70KD glycoprotein subunits. Hte epitopes recognizedthe three antibodies are diferent, but locate close to each other on the same molecules whichdistribute in the intracellular secretory canaliculi and cytoplasmic tubulovesicules, relating to HCl production. It is the next important problem whether autoreactive T and B cells are activated by recognizing the same epitopes of not.
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