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

Neil Andrew Marshall, Dominic J. Culligan, Peter W. Johnston, Colin Millar, Robert N. Barker, Mark A. Vickers

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalBritish Journal of Haematology
Volume139
Issue number1
Early online date11 Sep 2007
DOIs
Publication statusPublished - Oct 2007

Keywords

  • helper T cell
  • regulatory T cell
  • infectious mononucleosis
  • non-Hodgkin lymphoma
  • Epstein-Barr virus
  • lymphoproliferative disease
  • gene-expression
  • antigen
  • lymphocytes
  • blood
  • immunotherapy
  • epitopes
  • protein
  • identification
  • generation

Cite this

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. / Marshall, Neil Andrew; Culligan, Dominic J.; Johnston, Peter W.; Millar, Colin; Barker, Robert N.; Vickers, Mark A.

In: British Journal of Haematology, Vol. 139, No. 1, 10.2007, p. 81-89.

Research output: Contribution to journalArticle

@article{a477d479a3514a3da1723d8a622e33c3,
title = "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",
abstract = "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.",
keywords = "helper T cell, regulatory T cell, infectious mononucleosis, non-Hodgkin lymphoma, Epstein-Barr virus, lymphoproliferative disease, gene-expression, antigen, lymphocytes, blood, immunotherapy, epitopes, protein, identification, generation",
author = "Marshall, {Neil Andrew} and Culligan, {Dominic J.} and Johnston, {Peter W.} and Colin Millar and Barker, {Robert N.} and Vickers, {Mark A.}",
year = "2007",
month = "10",
doi = "10.1111/j.1365-2141.2007.06765.x",
language = "English",
volume = "139",
pages = "81--89",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - CD4(+) T-cell responses to Epstein-Barr virus (EBV) latent membrane protein 1 in infectious mononucleosis and EBV-associated non-Hodgkin lymphoma

T2 - Th1 in active disease but Tr1 in remission

AU - Marshall, Neil Andrew

AU - Culligan, Dominic J.

AU - Johnston, Peter W.

AU - Millar, Colin

AU - Barker, Robert N.

AU - Vickers, Mark A.

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - helper T cell

KW - regulatory T cell

KW - infectious mononucleosis

KW - non-Hodgkin lymphoma

KW - Epstein-Barr virus

KW - lymphoproliferative disease

KW - gene-expression

KW - antigen

KW - lymphocytes

KW - blood

KW - immunotherapy

KW - epitopes

KW - protein

KW - identification

KW - generation

U2 - 10.1111/j.1365-2141.2007.06765.x

DO - 10.1111/j.1365-2141.2007.06765.x

M3 - Article

VL - 139

SP - 81

EP - 89

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -