2007 Fiscal Year Final Research Report Summary
Vaccination With Autoreactive CD4^+Th1 Clones in Lupus-Prone MRL/Mp - Fas^<lpr/lpr> Mice
| Project/Area Number |
17591039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kyoto University |
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Principal Investigator |
FUJII Takao Kyoto University, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Lecturer (70255462)
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| Co-Investigator(Kenkyū-buntansha) |
MIMORI Tsuneyo Kyoto University, Department of Rheumatology and Clinical Immunology, Graduate Schcool of Medicine, Professor (10157589)
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| Project Period (FY) |
2005 – 2007
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| Keywords | svstemic lupus erytematosus / autoreactive T cells / T cell vaccination / T cell receptor |
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| Research Abstract |
Objective. To examine the efficacy of T cell vaccination with lupus autoantigen-specific CD4^+αβTh1 clones in lupus-prone MRL/Mp- Fas^<lpr/lpr> (MRL/lpr) mice.
Methods. By limiting dilution method, the autoreactive CD4^+ab Th1 clones, dna51 (Vb8.3) and rnp2 (Vβ14), which stimulated anti-dsDNA or RNP antibody (Ab) production respectively, were isolated from splenocytes of MRL/lpr mice. After adoptive transfer of the stimulated with IL-2 (s-) or irradiated (i-) clones to female 3-week old MRL/lpr mice, antinuclear antibody kinetics, renal function, renal histological changes, and lymphocyte subpopulations in splenocytes were examined. Anti-idiotypic humoral and T cell responses against the transferred autoreactive Th1 clones were also determined.
Results. Anti-dsDNA Ab titer, serum creatinine, and activity index for lupus nephritis were significantly suppressed in the i-dna51-received MRL/lpr mice in comparison with in the PBS-treated MRL/lpr mice. B and CD4^+Vβ8.3 T cell numbers in splenocytes were significantly decreased in the i-dna51-received MRL/lpr mice. Anti-idiotypic antibodies that recognized 12 amino acid residues of the clone dna51 Vb8.3-CDR3 and suppressed dna51 proliferation, and cytotoxic CD8^+T cells against dna51, were detected in the i-dna51-received MRL/lpr mice.
Conclusions. Vaccination with lupus autoantigen-reactive CD4^+ αβT cells may have the beneficial effects in MRL/lpr mice. Anti-idiotypic T cell and humoral responses against the clone dna51 might suppress not only the anti-dsDNA Ab production but also lupus nephritis.
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