| Project/Area Number |
05557079
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Morphological basic dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HAYASHI Yoshio Department of Pathology, School of Dentistry, The University of Tokushima, Professor, 歯学部, 教授 (00127854)
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| Co-Investigator(Kenkyū-buntansha) |
HAMANO Hironori Department of Pathology, School of Dentistry, The University of Tokushima, Resea, 歯学部, 助手 (10238074)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1993: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Sjogren's syndrome / Animal model / T cell receptor / Cytokine / MRL / lpr mice / NFS / sld mice / Autommunity / RT-PCR / lprマウス / シェーグレン症候群 / SCIDマウス |
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| Research Abstract |
We have established a new animal model for human primary Sjogren's syndrome in NFS/sld mutant mice bearing autosomal recessive gene with sublingual gland differentiation arrest. Significant inflammatory changes develop spontaneously in both the salivary and lacrimal glands of NFS/sld mutant mice thymetomized 3 days after birth without later immunization, whereas no inflammatory lesions were found in other organ in general. This pathology resembles primary Sjogren's syndrome involving the parotid, submandibular salivary gland and lacrimal gland. A significantly higher incidence of autoimmune lesions in females was found, and the antisalivary duct anibody was frequently detected in sera from mice with autommune lesions, but not in control mice. The inflammatory infiltrates in the salivary and lacrimal glands consisted mainly of CD3^+, CD4^+ T cells with lesser proportion of CD8^+ T cells, and B220^+ B cells. Mac-1^+ cells were occasionally found within these lesions. When the repertoire of T cell receptor (TCR) Vbeta genes transcribed and expressed within the inflammatory infiltration was analyzed in mice with autommune lesions, a preferential utilization of TCR Vbeta gene (vbeta8>Vbeta6) was detected in these lesions during the course of disease. Moreover, we succeeded in adoptive transfer of Sjogren's syndrome in MRL/lpr mice into SCID mice by intraperioneal injection using the salivary gland inflammatory cells. The treament with anti-CD4 and anti-Vbeta8 prevented the adoptive transfer into SCID mice. We concluded that murine autoimmune lesions developping in the salivary and lacrimal glands are obvious to depend on T-cell dependent immune response, and therapies designed with similar approaches might be used to prevent autoimmune diseases.
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