Characterization of the CD4+ T cell response to Epstein-Barr virus during primary and persistent infection.
The CD8+ T cell response to Epstein-Barr virus (EBV) is well characterized. Much less is known about the evolution of the CD4+ T cell response. Here we show that EBV stimulates a primary burst of effector CD4+ T cells and this is followed by a period of down-regulation. A small population of EBV-specific effector CD4+ T cells survives during the lifelong persistent phase of infection. The EBV-specific effector CD4+ T cells accumulate within a CD27+ CD28+ differentiation compartment during primary infection and remain enriched within this compartment throughout the persistent phase of infection. Analysis of CD4+ T cell responses to individual epitopes from EBV latent and lytic cycle proteins confirms the observation that the majority of the effector cells express both CD27 and CD28, although CD4+ T cells specific for lytic cycle antigens have a greater tendency to express CD45RA than those specific for the latent antigens. In clear contrast, effector CD4+ T cells specific for cytomegalovirus (CMV) accumulate within the CD27- CD28+ and CD27- CD28- compartments. There are striking parallels in terms of the differentiation of CD8+ T cells specific for EBV and CMV. The results challenge current ideas on the definition of memory subsets.
Amyes
Elisabeth
E
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, OX3 9DS Oxford, United Kingdom.
Hatton
Chris
C
Montamat-Sicotte
Damien
D
Gudgeon
Nancy
N
Rickinson
Alan B
AB
McMichael
Andrew J
AJ
Callan
Margaret F C
MF
D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003587:Cytomegalovirus / Q000276:immunology; D000939:Epitopes; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D010641:Phenotype; D016176:T-Lymphocyte Subsets; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology
D018106:CD28 Antigens; D000939:Epitopes; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014764:Viral Proteins; D017493:Leukocyte Common Antigens