2006 Fiscal Year Final Research Report Summary
Induction of human cytotoxic T cells by peptide-pulsed universal antigen presenting cells
| Project/Area Number |
16390294
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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 |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
TSUCHIYA Shigeru Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30124605)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAKI Satoru Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (20311566)
MINEGISHI Masayoshi Tohoku University, Hospital, Associate Professor, 病院・助教授 (20211592)
SASAHARA Yoji Tohoku University, Hospital, Research Associate, 病院・助手 (60372314)
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| Project Period (FY) |
2004 – 2006
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| Keywords | peptide antigens / B-LCL / cytotoxic T cells / tetoramer / EBV |
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| Research Abstract |
We examined the presence of EB virus (EBV) specific cytotoxic T cells, induction of EBV specific CTLs and the cytotoxic activities of induced CTLs in the peripheral CD8+ cells from the patient with chronic active EBV infection (CAEBV) and the results were as follows,
1.Demonstration of EBV specific CTLs by HLAA24-specific and EBV-specific tetramer analysis
BRLF1 peptides specific CTLs were found in the peripheral lymphocytes of healthy volunteers and those of patients with infectious mononucleosis. Interestingly, we were also able to demonstrate BRLF1 peptides specific CTLs in the peripheral blood of the patients with CAEBV.
2.Induction of antigen specific CTLs :
We used HLAA24 positive autologous B lymphobastoid cells (B-LCLs) as antigen presenting cells and peripheral mononuclear cells were stimulated with B-LCLs, pulsed with or without BRLF1 peptide. We were successfully able to induce BRLF1 tetramer positive CTLs even in the absence of BRLF1 specific peptides. This suggested that enoug
… More
h BRLF1 specific stimulation were given from the EBV infected B-LCLs to specific CTLs without further peptide pulse. These CD8 positive BRLF1 tetramer specific induction and proliferation of CTLs were observed in the mononuclear cells from both healthy volunteers and the CAEBV patient.
3.Cytotoxic activity of induced CTLs using interferon gamma producing ability of CTLs :
Then we examined the cytotoxic activities of induced CTLs. First we confirmed that BRLF1 tetramer specific CD8+ CTLs from healthy volunteers could produce interferon gamma only after BRLF1 specific peptides. We found that the mononuclear cells from a CAEBV patient also produce BRLF1 tetramer specific CTLs after stimulation with specific peptides. However, BRLF1 specific CTLs from the patient produced interferon gamma only approximately 30%, as compared with those from the healthy volunteers approximately 50%.
These results indicated the possibility that mononuclear cells from both healthy volunteers and the CAEBV patients are able to induce and proliferate specific CTLs, but cytotoxic activities of specific CTLs from the patient is reduced as compared with those of healthy volunteers. To elucidate the mechanism of the reduced CTL-activity of the CAEBV patient will have great implications to understand the etiology of CAEBV and the CTL therapy. Less
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