Nasopharyngeal carcinoma-associated Epstein-Barr virus-encoded oncogene latent membrane protein 1 potentiates regulatory T-cell function.
Sequence variation in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) oncogene structure may affect antigen-presenting cell (APC) function of infected B cells and immune escape by EBV-specific T cells and thus contribute to the development of malignancy. Normal B cell-associated LMP1 (B-LMP1) upregulates B cell APC function through activation of the necrosis factor (NF)-kappaB subunit, RelB. We examined the ability of B-LMP1 and a nasopharyngeal carcinoma-associated LMP1 (NPC-LMP1) to modulate B cell APC function and T-cell responses. B lymphoma cells transfected with NPC-LMP1 stimulated resting T cells in mixed lymphocyte reaction less efficiently than B-LMP1 transfectants. Unexpectedly, antigen presentation to CD4(+) T helper cells was reduced owing to potentiation of regulatory T-cell function by NPC-LMP1 transfectants, which produce increased levels of interleukin-10, rendering CD4(+) T cells hyporesponsive. Thus, after primary EBV infection, T cells may escape activation by NPC-LMP1. These observations have important implications for the establishment of EBV-associated malignancy in the context of infection with tumour-associated EBV LMP1 variants.
Pai
Saparna
S
Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia.
O'Sullivan
Brendan
B
Abdul-Jabbar
Ibtissam
I
Peng
Judy
J
Connoly
Geoff
G
Khanna
Rajiv
R
Thomas
Ranjeny
R
D000938:Antigen-Presenting Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000276:immunology*; D021381:Protein Transport / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014763:Viral Matrix Proteins / Q000276:immunology*
D015704:CD4 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D016753:Interleukin-10