Project/Area Number |
10044299
|
Research Category |
Grant-in-Aid for Scientific Research (B).
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | EHIME UNIVERSITY |
Principal Investigator |
ASANO Yoshihiro EHIME UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (70114353)
|
Co-Investigator(Kenkyū-buntansha) |
KUBO Shuichi TOKYO METROPOLITAN MEDICAL RESEARCH INSTITUTE RESEARCH FELLOW, 研究員 (00251223)
NAKAYAMA Toshinori CHIBA UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (50237468)
SHINOMIYA Hiroto EHIME UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80162618)
ALFRED Singer 米国国立癌研究所, 実験免疫部門, 部門長
RICHARD J. Hodes 米国国立加齢医学研究所, 所長
SINGER Alfre 米国国立癌研究所, 実験免疫部門, 部門長
HODES Richar 米国国立加齢医学研究所, 所長
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | infection immunity / innate immunity / T cell subset / IL-12 p40 / macrophage function |
Research Abstract |
Successful development of Th2 cells requires both differentiation and expansion processes, and depends on the activation levels of IL-4 receptor (IL-4R) -mediated signaling. Among signaling molecules downstream of IL-4R, STAT6 activation is thought to be critical for differentiation process, and phosphorylation of IRS-2 is important for proliferation. The activation of Ras/MAPK cascade appears to act on Jak1 kinase to enhance its kinase activity and improve IL-4R function. The activation of CN in naive CD4 T cells induces transcriptional upregulation of Jak3. STAT5 is found to be physically and functionally associated with IL-4 receptor complex in the anti-TCR-activated naive T cells and established cloned Th2 cells. The IL-4-induced activation of STAT5 appears to play an important role in the expansion process of the developing Th2 cells. Thus, the recruitment of Jak3 and STAT5 molecules to functional IL-4R complex in developing Th2 cells appears to be crucial for Th2 cell development. We demonstrated that the splenomegaly associated with Salmonella-infection, a host-defensive response, was caused by the migration of Mac-1^+ cells into the infected spleen. We tried to generate murine bone marrow-derived DC lines by using a helper-free and replication-defective recombinant retrovirus encoding the SV40 early antigens, and obtained several DC lines that can cytokine-independently grow. We established the mutant Listeria monocytogenes which expressed ply118 gene product when virulence genes are activated. We tried to establish the gene transduction system using this mutant Listeria.
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