| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
By repeating backcrosses 12 times, we introduced the lpr<@D1cg@>D1 gene from CBA/Kljms-lor<@D1cg@>D1/lpt<@D1cg@>D1 into MRL/MpJ and have obtained the congenic MRL/MpJ-lpr<@D1cg@>D1/lpt<@D1cg@>D1 mice (MRL-lpr<@D1cg@>D1) which exhibit prominent autoimmune diseases. By feeding from FM mother mice, we infected the neonatal MRL-lpr<@D1cg@>D1 with MMTV (FM) (MRL-lpr<@D1cg@>D1 fFM) which has a superantigen activity The validity of this system was confirmed by the demonstration of MMTV gp52 in their milk. First, the longevity of MRL-lpr<@D1cg@>D1 fFM was found to be longer (226(]SY.+-。[)15 days) than that of MRL-lpr<@D1cg@>D1 mice (180(]SY.+-。[)15days). Second, the weights of subcutaneous, internal and mesenteric lymph nodes in mice of both sexes at 3 mo and 5 mo were smaller in MRL-lpr<@D1cg@>D1 fFM than in MRL-lpr<@D1cg@>D1 mice. Flow cytometric analysis revealed the specific decrease in Vbeta8.2 and 14 cells in the lymphoid cells of MRL-lpr<@D1cg@>D1 fFM.Urinary protein as scored by our method was 2.41 (]SY.+-。[) 0.26 and 1.67 (]SY.+-。[) 0.16 in MRL-lpr<@D1cg@>D1 and MRL-lpr<@D1cg@>D1 fFM,respectively, of the male sex at 5 mo, and, 2.63 (]SY.+-。[) 0.24 and 2.08 (]SY.+-。[) 0.27 in MRL-lpr<@D1cg@>D1 and MRL-lpr<@D1cg@>D1 fFM,respectively, of the female sex at 5 mo. Histological exam utilizing H-E stained kidney sections revealed the lesser degree of glomerulonephritis in MRL-lpr<@D1cg@>D1 fFM than in MRL-lpr<@D1cg@>D1. Hence, it was inferred that the mice infected with MMTV (FM) showed the amelioration of mortality, lymph node enlargement and immune-complex glomerulonephritis due to the decrease or lack of Vbeta8.2 cells that are regarded to play a crucial role in murine autoimmune disease. We are now investigating kidney sections with electronmicroscopy and immunofluorescence, and also their sera for antinuclear antibodies, anti-DNA antibodies, immunoglobulins and circulating immune complexes.
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