| Project/Area Number |
16590454
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
KUDO Toyoichiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Lecturer (80324622)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
EGAWA Hiroto Kyoto University, Institute of Medical Science, Associate Professor. (40293865)
ICHIYAMA Satoshi Kyoto University, Institute of Medical Science, Professor (30223118)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | transplantation / regenerative medicine / infectious diseases / virus / histocompatibility antigen / tetrameric HLA / CMV / EBV / 移植・再生医療 / サイトメガロウイルス / EBウイルス / フローサイトメトリー / 細胞障害性リンパ球 / CD8 |
|---|
| Research Abstract |
Background : Organ recipients are at risk of herpes viruses infection, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Cytotoxic T-cells (CTL) are the pivotal component to control these viral infections. Tetrameric HLA (so-called tetramers) detect specific CTL against these viruses, and may help future adoptive therapy.
Aim : To evaluate tetramers as agents for monitoring CTLs, and to isolate and expand specific CTL for possible therapeutic purpose.
Methods : Sixty recipients of living liver graft were prospectively followed for 2-48 months. All had either of HLA A*0201 or A*2402, and corresponding tetramers were used to stain CTL. Viral DNA were monitored by real-time PCR. Samples with high viral load were assigned for isolation of specific CTLs by tetramers, and were incubated for expansion.
Results : A*0201 CMV pp65 tetramer detected CTL more efficiently than A*2402 CMV pp65 tetramer, even though the frequency of CMV infection was similar in both of A*0201 recipients and A*2402 recipients. In the presence of CMV DNAemia, A*0201 CMV pp65 tetramer found CTL in 100% of recipients, whereas only 46% in case of A*2402 CMV pp65. Severity of infection was similar irrespective of CTL detection by tetramers. Similar results were obtained for EBV.Expansion of CTL failed although the amounts of CTL were higher when viral loads were high.
Interpretation : Tetrameric HLA detects only a part of whole anti-viral CTL, which makes it difficult to apply tetramer detection of CTL for predictor of infection prognosis. Isolation of specific CTL failed partly due to scarcity of appropriate samples. An analysis of risk factors of CMV infection was done to add a new point of view for prognosis of infection.
|
