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Innate immune control of EBV-infected B cells by invariant natural killer T cells
- Source :
- Blood. 122:2600-2608
- Publication Year :
- 2013
- Publisher :
- American Society of Hematology, 2013.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....d93fcf1656f594d0d1ae2e84882a6a1d