Postexposure vaccination massively increases the prevalence of gamma-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 day s after respiratory challenge with the murine gamma-herpesvirus 68 (gamma H V-68), then develop symptoms of a progressive wasting disease. The gamma HV -68-specific CD8(+) T cells that persist in these I-A(b-/-) mice are unable to prevent continued, but relatively low level, virus replication. Postexp osure challenge with recombinant vaccinia viruses expressing gamma HV-68 ly tic cycle epitopes massively increased the magnitude of the yHV-68-specific CD8(+) population detectable by staining with tetrameric complexes of MHC class I glycoprotein + peptide, or by interferon-gamma production subsequen t to in vitro restimulation with peptide. The boosting effect was comparabl e for yHV-68-infected I-A(b-/-) and I-Ab(+/+) mice within 7 days of challen ge, and took more than 110 days to return to prevaccination levels in the I -Ab(+/+) controls. Although the life-span of the I-A(b-/-) mice was signifi cantly increased, there was no effect on long-term survival. A further boos t with a recombinant influenza A virus failed to improve the situation. Ons et of weight loss was associated with a decline in gamma HV-68-specific CD8 (+) T cell numbers, though it is not clear whether this was a cause or an e ffect 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 gamma HV-68 infection under conditions of CD4(+) T cell deficiency.