1. The relationships between Epstein-Barr virus latent membrane protein 1 and regulatory T cells in Hodgkin's lymphoma
- Author
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Marshall, Neil A., Culligan, Dominic J., Tighe, Jane, Johnston, Peter W., Barker, Robert N., and Vickers, Mark A.
- Subjects
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EPSTEIN-Barr virus , *T cells , *HODGKIN'S disease , *IMMUNOTHERAPY - 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 (3H-thymidine incorporation) and cytokine (interleukin [IL]-10, IL-4 and γ-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. [Copyright &y& Elsevier]
- Published
- 2007
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