Abstract | OBJECTIVE: Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability of LMP1 to stimulate regulatory T (Treg) responses in healthy donors, we hypothesized that LMP1 was important in the generation of Treg responses in HL. METHODS: We compared T helper (Th) 1, Th2, and Treg responses to LMP1 by peripheral blood mononuclear cells (PBMCs) and HLILs from EBV-positive and -negative HL patients. The number of Treg cells in patients' PBMCs and HLILs was determined by flow cytometry ex vivo. Proliferation ((3)H-thymidine incorporation) and cytokine ( interleukin [IL]-10, IL-4 and gamma-interferon) secretion by LMP1-stimulated PBMCs and HLILs was also measured. RESULTS: Ex vivo EBV-positive HL patients had increased numbers of IL-10-secreting/cytotoxic T-lymphocyte-associated antigen-4-expressing cells compared with EBV-negative HL patients. PBMC/HLIL responses to LMP1 from most patients were characterized by IL-10 secretion, although isolated HL patients mounted Th1-like responses. Several responses to LMP1 peptides were made by HLILs, which were otherwise unresponsive to control stimuli. CONCLUSIONS: These results suggest that LMP1 epitopes can induce HLIL Treg cells. However, there was no clear evidence of a greater bias toward regulation in EBV-positive HL cases over EBV-negative cases, and thus there are likely to be other mechanisms of Treg cell induction in EBV-negative HL patients. Manipulating the balance of T-helper response to LMP1 might be exploited in immunotherapy of these lymphomas.
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Authors | Neil A Marshall, Dominic J Culligan, Jane Tighe, Peter W Johnston, Robert N Barker, Mark A Vickers |
Journal | Experimental hematology
(Exp Hematol)
Vol. 35
Issue 4
Pg. 596-604
(Apr 2007)
ISSN: 0301-472X [Print] Netherlands |
PMID | 17379070
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- EBV-associated membrane antigen, Epstein-Barr virus
- Viral Matrix Proteins
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Topics |
- Adult
- Cell Proliferation
- Cytokines
(metabolism)
- Female
- Herpesvirus 4, Human
(isolation & purification)
- Hodgkin Disease
(immunology, physiopathology, therapy, virology)
- Humans
- Male
- Middle Aged
- T-Lymphocytes, Regulatory
(immunology, metabolism)
- Viral Matrix Proteins
(physiology)
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