| Project/Area Number |
10670428
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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 |
内科学一般
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| Research Institution | Teikyo University |
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Principal Investigator |
HIROHATA Shunsei Teikyou University, School of Medicine, Associate Professor, 医学部, 助教授 (90189895)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGIDA Tamiko Teikyou University, School of Medicine, Assistant, 医学部, 助手 (80082204)
HASHIMOTO Takashi Teikyou University, School of Medicine, Associate Professor, 医学部, 助教授 (30082142)
MIYASHITA Taku Teikyou University, School of Medicine, Assistant, 医学部, 助手 (00239401)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | IL-12 / IFN-γ / TH1 / Th2 / cyclin A / mizoribine / Fas / CD40L / anti-CD3 / CD4+T細胞 / 免疫グロブリン / 免疫抑制薬 / ミゾリビン / SLE / Fas / アポトーシス |
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| Research Abstract |
Although human T cells have been shown to regulate humoral immune responses by directly inhibiting B cells, the precise sequelae for the mechanism of suppression have not yet been delineated. The present study therefore examined the nature of T cell-B cell collaboration to suppress B cell responses. Special attention was directed to the role of Fas (CD95)-Fas ligand (FasL) interactions and CD40-CD40 ligand (CD40L) interactions. The results indicate that signals achieved by direct interactions through CD40-CD40L exert bidirectional effects on the outcome of humoral immune responses depending on the state of activation of B cells and on the extent of CD40 ligation. Moreover, the data suggest that CD40-CD40L interactions rather than Fas-FasL interactions may play more critical roles in direct cellular collaboration between B cells and anti-CD3 stimulated CD4+ T cells to prevent the extention of responses of inappmpriately activated B cells.
IL-12 is the prominent inducer of Th1 responses i
… More
n human and in the mouse. CD40L plays important roles in regulation of immune responses, including T cell-dependent activation of B cells and cytokine production by monocytes and dendritic cells. We next examined the influences of IL-12 on the CD40L expression a activated human CD4+ T cells. The results indicate that IL- 12 enhances the CD40L expression of activated CD4+ T cells independently of the IFN-γ production. The data thus suggest that Th1 responses induced by IL-12 might play an important role in regulation of humoral immune responses through up-regulated CD40L expression.
Mizoribine has been shown to have beneficial effects in the treatment of rheumatoid arthritis and lupus nephritis, in which abnormal B cell functions are involved. Previous studies demonstrated that mizoribine directly suppresses the function of human B cells. We explored in detail the mechanism of the suppression of human B cell responses by mizoribine at the molecular level. The results indicate that mizoribine suppresses the expression of cyclin A mRNA in human B cells by downregulating its stability, and thus downregulates their responses. Less
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