| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
We observed that several autoantibodies such as antinuclear antibody (ANA), anti-lactoferrin (LF) antibody (ALF), anti-carbonic anhydrase-II (CA-II) antibody (ACA-II ), rheumatoid factor and antismooth muscle antibody were frequently detected in patients with. The high prevalence of these antibodies suggests that CA-II and LF may be the candidates for the target antigens in AIP.Although the effector cells of AIP have been poorly understood, the activated CD4+ and CD8+ T-cells bearing HLA-DR and CD45RO were increased in the peripheral blood lymphocytes (PBLs) in the patients with AIP in comparison with those in other causes of pancreatitis such as alcoholic or gallstone-related pancreatitis. CD4+ T-cells also predominantly infiltrate in the pancreas tissue over CD8+ T-cells. Similar to SjS or PSC, CD4+ T-cells showing Th1 type of immune response are predominantly involved in the development of AIP as effector cells over Th2 type CD4+ T-cells. In some patients with AIP, HLA-DR antigens a
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re expressed on the pancreatic duct cells as well as CD4+ T-cells. Neonatally thymectomized (nTx) mice subcutaneally immunized with CA-II or LF, and synergetic nude mice, transferred with seplenocytes from the disease-induced nTx-mice, developed pancreatitis as well as sialoadenitis and cholangitis, but the normal BALA/c mice did not. In our animal model using nTx-BALB/c mice and transferred nude mice, the CD4-positive cells were mainly involved in the development of pancreatitis, sialoadenitis and cholangitis, while CD8+ T-cells were never pathogenic. These findings suggested that MHC-class II restricted-autoreactive CD4+T-cells, which escape from the negative selection in the thymus, and depletion of regulatory T-cells such as CD25+ T-cells in the periphery take important roles in the development of autoimmune pancreatitis and exocrinopathy. These animal models suggest that although CD8+ T-cells may be partially involved, CD4+ T-cells take major roles in the development of experimental pancreatitis, which is consistent with human AIP. Less
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