Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution Keio University
2.Research Area Life Sciences
3.Research Field Infectious Diseases and Bioregulation
4.Term of Project FY 1997 〜 FY 2001
5.Project Number 97L00701
6.Title of Project Functional Analysis of Cellular Immunity in Infectious Diseases

7.Project Leader
Name Institution,Department Title of Position
Shigeo, Koyasu Keio University, School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Yasuo, Ikeda Keio University, School of Medicine Professor
Hiromichi, Ishikawa Keio University, School of Medicine Professor
Tsutomu, Takeuchi Keio University, School of Medicine Professor

9.Summary of Research Results

1) Contrary to the current model that interferon-γ (IFN-γ) is during early phase of infection produced by natural killer (NK) cells in response to IL-12 produced by antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages, we revealed that interferon-γ (IFN-γ) is produced by APCs in response to IL-12 produced by themselves upon microbial infection. It is likely that APCs play a pivotal role in innate immune responses against microbial infection by producing IFN-γ in an autocrine manner.
2) Using Leishmania major infection, it was demonstrated that a genetic factor(s) determining Th1 vs. Th2 responses against L. major is carried by DCs. Phosphoinositide 3-kinase (PI3K) was shown to be involved in Th1/Th2 regulation.
3) We showed that PI3K is critical in B cell development and functions. Furthermore, we demonstrated that PI3K is essential for the development of gastrointestinal mast cells and immunity against intestinal nematode infection.
4) We identified "cryptopatches" in both small and large intestines, as anatomical sites for differentiation of intestinal intraepithelial lymphocytes in the gut. Each cryptopatch contains 〜1000 c-kit+ progenitor cells that are capable of differentiating into T cells.

10.Key Words

(1)microbial infection、(2)innate immunity、(3)dendritic cell
(4)interferon-γ、(5)type-1 helper T cell、(6)type-2 helper T cell
(7)mast cell、(8)intestinal intraepithelial cell、(9)knockout mouse