| Project/Area Number |
09670336
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
KINA Tatsuo Kyoto University, Institute for Frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (30127071)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | pre-T cell / cell differentiation / thymus / signal transduction / G-protein / integrin / T細胞 / モノクローナル抗体 / クローン / ヘテロ三量体G蛋白質 / 百日咳菌毒素 / コレラ菌毒素 |
|---|
| Research Abstract |
The present study aimed to explore the molecular mechanisms of growth and differentiation of early T cells in the thymus. For this purpose, we introduced a stromal-cell dependent pre-T cell clone (BTK-24) as an in vitro model for pre-T cell development. BTK-24 is a typical pre-T cell clone with a rearranged TCRbeta gene and germline TCRalpha genes. Growth of BTK-24 requires direct cell contact with stromal cells, although a kind of solube mediator(s) released from stromal cells is also involved for optimal growth. We found that adhesion between BTK-24 and stromal cells is mediated by VLA-4/VCAM-1 interaction. The soluble mediator involved in pre-T cell growth appears to be a small chemokine-like molecule, because its activity was lost by dialysis, and because stimulation with IL-1, TNFalpha or LPS greatly increased the growth promoting activity of the mediator. A low dose of pertussis toxin (PTX) is highly suppressive for BTK-24 growth, suggesting that inhibitory G-protein alpha (Galphai )-mediated signal pathway is important for growth. It was also demonstrated that co- culture of TK-24 with primary thymic stromal cell monolayer resulted in the induction of CD3/TCR complex and CD4 antigen on BTK-24 cells. These results suggest that both direct (adhesion) and indirect (cytokine) interactions 'with stromal cells are important for pre-T cell growth, and that some stromal cells in the thymus has ability to induce the differentiation of pre-T cells.
|
