| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Autoimmune diseases result from self-tissue destruction caused by auto-reactive immune responses which are not elicited in normal human and mine. We have analyzed immunological abnormalities in autoimmune-prone MRL/lpr mice, particularly graft-versus-host disease (GVHD) -like disorders obeserved in [MRL/lpr -> MRL/+] bone marrow chimeras. In these studies, two interesting monoclonal autoantibodies (25T3 and F6C7) reactive with white blood cells have been established. 25T3 monoclonal antibody (mAb) (IgM,k) is specific for T cells, and reacts to 70-80% peripheral CD8^+ T cells and 30% peripheral CD4^+ T cells. 25T3^+CD4^+T cells secret more IL-2 than 25T3^-CD4^+T cels, and 25T3^-CD4^+T cells secret more IL-4 than 25T3^+CD4^+T cells after in vitro stimulation with anti-CD3 mAb. Therefore, 25T3 mAb may divide CD4^+T cells into Th1 and Th2 subpopulaitons. The 25T3-reactive antigen is approximately 70 kDa. F6C7 mAb (IgG2b, k) strongly reacts to blastic T cells activated by autologous MLR and
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some blastic T cells of MRL/lpr mice. The F6C7-reactive antigen is a heterodimer of approximately 78 and 70 kDa. Although these antigens are not cloned, these mAbs are usuful for analyzing T cell abnormalities in immunological disorders. We have further established nephritogenic mAbs from FGS or (NZW X BXSB) F1 mice which spontaneously develop glomerulonephritis. When the mAbs are transplanted into SCID mice, the mice show proteinuria and glomerulonephritis. FG1H5 mAb (IgM,k) reacts both ssDNA and glomerulus (mainly mesangium), and deposits in the glomeruli. The FG1H5 reactive antigen is approximately 28 kDa. W/B4A9 mAb (IgM,k) deposits along systemic capillary walls in cluding kidney, heart and etc. The mAb reacts to approximately 25 kDa plasma protein. W/B2A4 mAb (IgG3, k) is a cryoglobulin, deposits mainly in glomerular capillary walls and induced high level of proteinuria. These nephritogenic mAbs may elucidate the nephritogenic antigens and contribute to understanding the mechanisms underlying the development of glomerulonephritis. Less
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