2012 Fiscal Year Final Research Report
The manufacture of the EBV-T/NK LPD model mouse and the study of the clinical condition expression mechanism
| Project/Area Number |
22590374
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | National Research Institute for Child Health and Development |
|---|
Principal Investigator |
IMADOME Ken-ichi 独立行政法人国立成育医療研究センター, 母児感染研究部, 室長 (70392488)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | 疾患モデル動物 |
|---|
| Research Abstract |
Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients’ PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rcnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Transplantation of individual immunophenotypic subsets isolated from patients’ PBMC as well as that of various combinations of these subsets revealed a critical role of CD4_+T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4_+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases.
|
