Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers

Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers
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DOI:
10.1182/blood-2006-05-023663
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发表时间:
2007-02-01
期刊:
影响因子:
20.3
通讯作者:
Munz, Christian
Munz, Christian
中科院分区:
医学1区
文献类型:
--
作者:
Heller, Kevin N.;Upshaw, Jenica;Munz, Christian

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CD4(+) T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4(+) T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4(+) T cells at a frequency of 0.03% of circulating CD4(+) T cells. In addition, healthy carriers have a large pool of CD4(+) T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4(+) T cells belonged to the central-memory compartment (T-CM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (T-EM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific T-CM CD4(+) T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of T-CM CD4(+) TH1 precursors, which continuously fuels TH1-polarized effector cells.