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CD4 + T‐cell responses to Epstein–Barr virus (EBV) latent membrane protein 1 in infectious mononucleosis and EBV‐associated non‐Hodgkin lymphoma: Th1 in active disease but Tr1 in remission
Author(s) -
Marshall Neil A.,
Culligan Dominic J.,
Johnston Peter W.,
Millar Colin,
Barker Robert N.,
Vickers Mark A.
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06765.x
Subject(s) - mononucleosis , immunology , lymphoma , virus , effector , asymptomatic , epstein–barr virus , virology , herpesviridae , t cell , medicine , virus latency , biology , viral disease , immune system , viral replication
Summary Primary infection with Epstein–Barr virus (EBV) in childhood is usually asymptomatic, whereas infection in adolescence may result in infectious mononucleosis (IM) often followed by a fatigue syndrome. EBV latent membrane protein 1 (LMP1) is expressed in latency and in many EBV‐associated tumours, including non‐Hodgkin lymphoma (NHL). Given the regulatory nature of the CD4 + T‐cell response against LMP1 previously reported in healthy donors, we investigated whether patients with active EBV‐driven disease can nevertheless mount effector [T‐helper cell, type 1 (Th1)] anti‐LMP1 responses. We therefore performed a longitudinal study of the nature of CD4 + T‐cell responses to LMP1 in four patients with IM, and five patients with NHL. In both groups, responses changed with time. During symptomatic infection or active tumour growth, responses were dominated by a Th1 effector phenotype, but switched to a regulatory interleukin‐10 response upon recovery. In addition, the fine specificities of the T cells driving these responses evolved. This study showed the dynamic nature of CD4 + T‐cell responses to LMP1, and demonstrated that, although patients can mount Th1 effector responses, recovery from IM and NHL is associated with regulatory responses.