| Project/Area Number |
13670454
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HORI Toshiyuki Kyoto University, Dept. Hematol. & Oncol., Lecturer, 医学研究科, 講師 (70243102)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | OX40 / OX40 ligand / gp34 / Bone marrow transplantation / GVHD / Allo reactivity / Dendritic cell / CD4 / T細胞 / GVHD / 造血幹細胞移植 |
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| Research Abstract |
We studied the role of the OX40/OX40L in GVHD that is though to be ascribed to alloreactive immune response of donor-derive T cells to recipient cells.
We examined the expression of OX40 on peripheral blood T cells of post-stem cell transplantation patients after day 100. The percentages of both OX40^+CD4^+ and OX40^+CD8^+ T cells were significantly higher in patients with chronic c GVHD than those without. Serial analyses showed that OX40^+CD4^+ T cells elevated before the onset of cGVHD and at the onset closely correlated with the therapeutic response. These results indicated that serial measurement of OX40^+ T cells is useful for predicting the onset as well as therapeutic response of cGVHD and raised a possibility that the OX40/gp34 system is involved in the pathogenesis of cGVHD (Blood 98:3162, 2001). To define the role of the OX40/OX40L system in alloreactivity in more detail, we examined the effect of anti-OX40L mAb on proliferative response of CD4^+ T cells to allogeneic monocyte-derived DCs. We observed that expression of OX40 was dependent on CD28 signals and anti-OX40L mAb markedly inhibited proliferative response of CD4^+ T cells to allogeneic DC and even to sorted OX40L^- DC, indicating that the OX40/OX40L system plays a crucial role in allogeneic T cell immune response (Immunology, 109:226-231, 2003). We found that OX40 signaling induces production of RANTES at both mRNA and protein levels by vascular endothelial cells, which we first identified in screening with cDNA array (Immunol. Lett. 84:1, 2002). Now that CCR5^+ T cells are considered to initiate GVHD (Nature Immunol. 4:154, 2003), this finding may be of pathophysiological relevance.
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