Analysis of the Mechanism of Induction of T cell development in the Thymus.
| Project/Area Number |
01480189
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
YOSHIMOTO Katsura Kyoto Univ., Chest Dis. Res. Inst., Professor, 胸部疾患研究所 (90027095)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Shinji Kyoto Univ., Chest Dis. Res. Inst. Assistant Prof., 胸部疾患研究所, 助手 (60199370)
KINA Tatsuo Kyoto Univ., Chest Dis. Res. Inst. Associate Prof., 胸部疾患研究所, 助教授 (30127071)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1990: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1989: ¥3,900,000 (Direct Cost: ¥3,900,000)
|
|---|
| Keywords | Thymus / T cell / Development / Stroma cells / Cytokine |
|---|
| Research Abstract |
This project aimed at investigating the mechanism of T cell differentiation and growth in the thymus, and the following points were clarified.
1. The most immature pre T cells in the thymus. The precursor activity of various subpopulations of thymus cells were investigated by transferring into deoxyguanosine (dGuo)-treated Fetal Thymus Organ Culture (FTOC) by micro i. T. Method (cell injection method with a microinjector). It was found that the pre T cells in thymic Thy-1^- cells were the most immature among those ever discovered, and it was suggested that they were the immediate progeny of the stem cells immigrated from the bone marrow.
2. Importance of macrophages (MUphi) in T cell growth. With micro i. T. Transfer system, it was shown that MUphi promoted the differentiation and/or growth of T cells in dGuo-FTOC. Dendritic cells (DC) were unable to play a similar role.
3. Binding of T lineage cells on the surface of stromal cells. We have succeeded in isolating a new cell surface molecule (107KDa glicoprotein) that mediates the binding between thymic fibroblastoid stromal cell lines and an immature T cell line. Using a monoclonal antibody to this molecule, studies are in progress to clarify the role of cell to cell interaction on T cell development.
4. Thymic stromal cell line and cytokines. A fibroblastoid stromal cell line TSt-4 derived from murine fetal thymus is able to support the growth of CD4^+ helper T cells from CD4^-8^- cells. Although TSt-4 synthesizes IL-7 and M-CSF, these cytokines themselves seemed unable to support the differentiation of CD4^+ T cells, suggesting the importance of cell to cell interaction or unknown factors.
5. Requirement of DC in intrathymic tolerance. Cells required for clonal deletion type tolerance to a superantigen Mls-1^a was investigated in micro i. T. System. It was found that DC and B cells were required. B cells played only to supply the Mls antigen, whereas DC were strongly suggested to be the effector cells.
|
Report
(3 results)
Research Products
(22 results)
