Innate immune control of EBV-infected B cells by invariant natural killer T cells
| Autor: | Peter van den Elzen, Frederick K. Kozak, Mohammad Rubayet Hasan, Brian K. Chung, Johnny C. Nie, Dong Jun Zheng, Lenka Allan, Catherine M. Biggs, Kevin Tsai, Rusung Tan, John J. Priatel |
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| Rok vydání: | 2013 |
| Předmět: |
Epstein-Barr Virus Infections
Herpesvirus 4 Human Lymphoid Enhancer-Binding Factor 1 Palatine Tonsil Immunology Cell Cell Communication Biology Biochemistry Antigen hemic and lymphatic diseases medicine Humans Receptor B cell B-Lymphocytes Innate immune system ZAP70 hemic and immune systems Cell Biology Hematology Natural killer T cell Immunity Innate Lymphoproliferative Disorders Cell Transformation Neoplastic medicine.anatomical_structure CD1D biology.protein Natural Killer T-Cells Antigens CD1d |
| Zdroj: | Blood. 122:2600-2608 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-01-480665 |
| Popis: | Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-α agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon γ secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition. |
| Databáze: | OpenAIRE |
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