Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of γ-Herpesvirus-Infected CD4-Deficient Mice

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Abstract
Mice (I-Ab−/−) that lack CD4+ T cells remain healthy for at least three months after respiratory exposure to the murine γ-herpesvirus 68 (γHV68), then succumb with symptoms of chronic wasting disease. Postexposure challenge of γHV68-infected I-Ab+/+ and I-Ab−/− mice with a recombinant vaccinia virus (Vacc-p56) expressing an antigenic γHV68 peptide caused a massive increase in the numbers of Dbp56-specific CD8+ T cells. Previous experiments showed that, despite the large numbers of potential CTL effectors, there was little effect on the long-term survival of the CD4-deficient group and no diminution in the level of persistent virus shedding and latency. Comparison of the expanded CD8+Dbp56+ sets in the I-Ab+/+ and I-Ab−/− mice indicated that these two T cell populations were not identical. More CD69highCD8+ Dbp56+ T cells were found in the CD4-deficient mice, an effect that might be thought to reflect higher Ag load. By contrast, the mean fluorescence intensity of staining for the CD44 glycoprotein was diminished on CD8+Dbp56+ T cells from the I-Ab−/− group, the level of CTL activity was lower on a per cell basis, and the relative prevalence of IFN-γ+TNF-α+ T cells detected after in vitro stimulation with the p56 peptide was decreased. Given that this experimental system provides an accessible model for evaluating postexposure vaccination protocols that might be used in diseases like HIV/AIDS, the further need is to clarify the underlying molecular mechanisms and the relative significance of lack of CD4+ T help vs higher Ag load for these expanded CD8+ effector populations.

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