A γ-herpesvirus sneaks through a CD8+ T cell response primed to a lytic-phase epitope
A γ-herpesvirus sneaks through a CD8+ T cell response primed to a lytic-phase epitope
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DOI:
10.1073/pnas.96.16.9281
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发表时间:
1999-08-03
影响因子:
11.1
通讯作者:
Doherty, PC
中科院分区:
文献类型:
--
作者:
Stevenson, PG;Belz, GT;Doherty, PC
To determine whether established CD8(+) T cell memory to an epitope prominent during the replicative phase of a gamma-herpesvirus infection protects against subsequent challenge, mice were primed with a recombinant vaccinia virus expressing the p56 peptide and then boosted by intranasal exposure to an influenza A virus incorporating p56 in the neuraminidase protein. Clonally expanded populations of functional, p56 specific CD8(+) T cells were present at high frequency in both the lung and the lymphoid tissue 1 month later, immediately before respiratory challenge with gamma HV-68, This prime-and-boost regime led to a massive reduction of productive gamma HV-68 infection in the respiratory tract and, initially, to much lo tr er levels of latency in both the regional lymph nodes and the spleen. The CD8(+) T cell response to another epitope (p79) was diminished, there was less evidence of B cell activation, and the onset of the CD4(+) T cell-dependent splenomegaly was delayed. Within 3-4 weeks of the gamma HV-68 challenge, however, the extent of latent infection in the lymph nodes and spleen was equivalent, and both groups developed the prominent infectious mononucleosis-like syndrome that is characteristic of this infection. The reverse protocol (influenza then vaccinia) seemed to be slightly less effective. Even though immune CD8(+) T cells may be present at the time and site of virus challenge, establishing a high level of CD8(+) T cell memory to lytic-phase epitopes alone does not protect against the longer-term consequences of this gamma HV infection.