2006 Fiscal Year Final Research Report Summary
Role of CD4O-CD4OL signaling in Epstein-Barr virus infection
| Project/Area Number |
17590427
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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 |
Virology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
IMADOME Ken-Ichi National Research Institute for Child Health and Development, Department of Infectious Diseases, Postdoctoral fellow, 母児感染研究部, 流動研究員 (70392488)
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| Project Period (FY) |
2005 – 2006
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| Keywords | EBV / CD40 / CD4OL |
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| Research Abstract |
We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus.
(1) Coexpression of CD40 and CD40L in EBV-infected T and NK cell lines derived from CAEBV and nasal T/NK cell lymphoma.
(2) Enhancement of apoptosis in EBV-infected T and NK cell lines by blockade of the interaction between CD40 and CD40L.
(3) Mediation by CD40 of protection from apoptosis.
(4) Mediation of a cell-survival signal by CD40 induced in Jurkat T cells, by EBV.
(5) Identification of EBV-infected T cells in peripheral blood from a patient with CAEBV and the role that CD40-CD40L signaling plays in their survival.
(6) XHIM-LCLs (established from X-linked Hyper IgM syndrome patients B cells) have the resistance for apoptosis less than normal-LCL.
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