| Project/Area Number |
09470090
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
NARIUCHI Hideo Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (10012741)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAMURA Toshiki Institute of Medical Science, The University of Tokyo, Assistant, 医科学研究所, 助手 (40291306)
YOSHIMOTO Takayuki Institute of Medical Science, The University of Tokyo, Assistant, 医科学研究所, 助手 (80202406)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥4,400,000 (Direct Cost: ¥4,400,000)
|
|---|
| Keywords | IL-12p35 / IL-2p40 / MHC class II / B7 / CD28 / CD152 / IL-12 independent TH1 differentiation / IL-12受容体 / IL-12Rβ2 / B7刺激 / トランスジェニックマウス / 副刺激 / T細胞抗原受容体 / T細胞上B7-2発現 |
|---|
| Research Abstract |
Differentiation and activation of Th cell sub Th1 is mainly regulated by IL-12. We, therefore, designed the present project to elucidate the regulation of IL-12 production and IL-12 receptor expression. IL-12 is composed of p35 and p40. We and other groups had shown that antigen-presenting cells (APC) produced p40 upon CD40 stimulation. In the present studies, we tried to identify the molecules on APC playing an important role in the p35 production. MHC class II molecules are revealed to be the molecule and p35 produced by the calss II stimulation contributed the bioactive IL-12 production. IL-12 receptor is also composed of β1 and β2 heterodimer. These components, especially β2, are expressed in T cells by B7 costimulation along with TCR ligation. The counter receptor for B7 on T cells playing a critical role in IL-12R expression was shown to be CD28. CD152, in contrast, was revealed to down regulate the expression. We also demonstrated that there is an IL-12 independent pathway for Th1 subset differentiation, that is, CD152 stimulation polarized naive T cells toward Th1 subset. CD152 was indicated to induce Th1 subset differentiation via unknown mechanism in addition to the suppression of IL-4 production and induction of TGF- β Production. We also examined whether IL-12 dependent Th1 polarization occurr in vivo by producing p40 transgenic mice. These mice showed the phenotype with Th2, dominant and impaired resistancy to malarial infection. These results showed that IL-12 actually, plays an important role in Th1 subset differentiation in vivo.
|
