2012 Fiscal Year Final Research Report
Novel mechanisms of alloreactive T-cell activation in GVHD and GVL
| Project/Area Number |
21390295
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Hokkaido University (2012)
Kyushu University (2009-2011) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Shuichirou 九州大学, 大学病院, 助教 (70622116)
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| Project Period (FY) |
2009 – 2012
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| Keywords | GVHD / GVL / T 細胞 / 樹状細胞 / 形質細胞様樹状細胞 / Toll like receptor |
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| Research Abstract |
We have identified two novel mechanisms of alloreactive T-cell activation in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic hematopoietic stem cell transplantation. First, besides conventional dendritic cells (DCs), plasmacytoid DCs can also fully activate alloreactive T cells to induce full spectrum of GVHD. This is dependent on pretransplant conditioning and MHC class II, but independent of toll-like receptor (TLR) signaling in pDCs. Second, TLR signaling in T cells are critical for activation of alloreactive T cells to induce GVHD and GVL. TLR signaling is important for activation, cytokine production, and cytolytic activity of both CD4+ and CD8+ T cells.
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