Analysis of T cell functions regulated by FOXP3, a causative
| Project/Area Number |
14570713
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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 |
Pediatrics
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KAWAMURA Nobuaki Hokkaido Univ., Grad.School of Med., Lec., 医学部・歯学部附属病院, 講師 (90301879)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Ichiro Hokkaido Univ., Grad.School of Med., 医学部・歯学部附属病院, 医員
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | IPEX / FOXP3 / regulatory T cell / 調節性T細胞 / 調整性T細胞 / T細胞活性化 / 転写因子 / 全身性自己免疫疾患 |
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| Research Abstract |
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a systemic autoimmune disease characterized by a wide variety of auto-antibodies, that is caused by a defect of FOXP3 gene, a possible transcription factor belonging to a forkhead/winged-helix family. In 2002, we studied in vivo/ in vitro immunological functions of a boy with IPEX carrying FOXP3-gene mutations. Both T and B cells from his peripheral blood expressed a high level of several activation markers and most of them showed a memory phenotype. Increased class-switching of B cells indicated an abnormally activated helper activity of T cells. Analysis of CD4-positive T cell lines established from peripheral blood of the patient revealed a high expression of CD13, increased cytokine productions, and a resistance to proliferation-inhibition effect of cyclosporin A.
In 2003, we made a rabbit anti-human FOXP3 polyconal antibody by using synthetic peptides for FOXP3. We analyzed the expression of FOXP3 during T cell activation by RT-PCR and Western blot. FOXP3 was already expressed in non-activated peripheral blood lymphocytes from normal individuals and we could not detect a obvious change of FOXP3-expression after T cell activation. We also tried an intracytoplasmic staining of FOXP3 using flow cytometry. We could detect a low level of positive signals in FOXP3-positive T cell lines using this method but not in peripheral blood lymphocytes from normal individuals. We also cloned FOXP3 mutations (small deletion and point mutation) detected in our two IPEX patients into retrovirus expression vectors and prepared the in vitro expression experiments.
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Report
(3 results)
Research Products
(12 results)
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[Publications] Kobayashi I, Reza Shiari, Yamada M, Kawamura N, Okano M, Yara A, Iguchi A, Ishikawa N, Ariga T, Sakiyama Y, Ochs HD, Kobayashi K: "Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX)."J Med Genet. 38. 874-876 (2001)
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Related Report
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[Publications] Nieves DS, Phipps RP, Pollock SL, Ochs HD, Zhu Q, Scott GA, Ryan C, Kobayashi I, Rossi TM, Goldsmith LA.: "Dermatologic and immunologic findings in the Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome."Arch Dermatol. 140. 466-472 (2004)
Description
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Related Report
