Postexposure vaccination massively increases the prevalence of γ-herpesvirus-specific CD8(+) T cells but confers minimal survival advantage on CD4-deficient mice

Mice that lack CD4(+) T cells remain clinically normal for more than 60 days after respiratory challenge with the murine γ-herpesvirus 68 (γHV-68), then develop symptoms of a progressive wasting disease. The γHV-68-specific CD8(+) T cells that persist in these I-A(b−/−) mice are unable to prevent continued, but relatively low level, virus replication. Postexposure challenge with recombinant vaccinia viruses expressing γHV-68 lytic cycle epitopes massively increased the magnitude of the γHV-68-specific CD8(+) population detectable by staining with tetrameric complexes of MHC class I glycoprotein + peptide, or by interferon-γ production subsequent to in vitro restimulation with peptide. The boosting effect was comparable for γHV-68-infected I-A(b−/−) and I-A(b+/+) mice within 7 days of challenge, and took more than 110 days to return to prevaccination levels in the I-A(b+/+) controls. Although the life-span of the I-A(b−/−) mice was significantly increased, there was no effect on long-term survival. A further boost with a recombinant influenza A virus failed to improve the situation. Onset of weight loss was associated with a decline in γHV-68-specific CD8(+) T cell numbers, though it is not clear whether this was a cause or an effect of the underlying pathology. Even very high levels of virus-specific CD8(+) T cells thus provide only transient protection against the uniformly lethal consequences of γHV-68 infection under conditions of CD4(+) T cell deficiency.