| Project/Area Number |
02670162
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
NAGATA Norikazu Kansai Medical University, 医学部, 講師 (40155940)
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| Co-Investigator(Kenkyū-buntansha) |
HISHA Hiroko Kansai Medical University, 医学部, 助手 (90151422)
TOKI Junko Kansai Medical University, 医学部, 助手 (40077681)
INABA Muneo Kansai Medical University, 医学部, 講師 (70115947)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | MRL / + mice / lpr mice / lpr-GVHD / Autoreactivity / MHC class II antigen / T cell clone / Autoantibody / Monoclonal antibody / lpr / GVHD / 自己MHC反応性 / T細胞クロ-ン / モノクロ-ナル抗体 / lprーGVHD / Autoreactive T cells / Autoanttdody |
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| Research Abstract |
Two congenic strains of MRL mice are knwon; MRL/lpr mice possess lpr gene and MRL/+ mice posses wild type gene. Although they are different at the presence of lpr gene, lethally irradiated MRL/+ mice reconstituted with MRL/lpr bone marrow cells develop severe graft-versus-host disease (GVHD)-like syndrome which is known as lpr-GVHD (1). We have established a CD4^+ T cell line (l/+T1) and examined characteristics of l/+T1 cells in vitro and in vivo.
1. L/+ T1 cells show prliferative response restricted to self-I-E^k molecule in vitro. B cells show relatively high stimulation activity to l/+T1 cells (2).
2. L/+T1 cells can induce proliferation and differentiation of I-E^k B cells, and induce lgM production including autoantibodies (anti-ssDNA antibodies and rheumatoid factors (RF) in vitro (2). 3. Injection of l/+T1 cells to H-2^k mice (MRL/+ and AKR), but not to H-2^d mice, induces enhanced autoreactivity of recipient spleen cells 1 to 2 months after injection. The injection also enhances
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IgG RF prosuction in MRL/+ mice, and slightly IgG and IgM RF production in AKR mice. However, anti-ssDNA antibody production can not be augmented by the injection of l/+ T1 cells, suggesting that autoantibody production is dependent on the presence of antigen (3).
4. When MRL/lpr abnormal T cells were co-cultured with l/+ T1 cells,
abnormal T cells showed a tendency to convert to CD8^+ T cells. However, the conversion was not so marked comparing with control cultures.
5. A hybridoma (25T3, IgM, k) was established from MRL/+ mice immunized with l/+T1 cells. 25T3 monoclonal antibody (mAb) is specific for T cells and reacts with approximately 90% thymocytes. In splenic T cells, approximately 90% CD8^+ cells are positive for 25T3-reactive antigen (25T3-Ag), and CD4^+ T cells are divided to two popualtions by their surface expression of 25T3-Ag; CD4^+25T3-Ag^+ cells relatively correspond to Thl cells and CD4^+25T3^- cel'ls to Th2 cells. 25T3-Ag is approximately 70 kDa by SDS-PAGE. L/+ T1 cells are positive for 25T3-Ag, 25T3 mAb may be useful to analyze autoimmune disease and lpr-GVHD (4). Less
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