Virus-specific CD8(+) T cell numbers are maintained during γ-herpesvirus reactivation in CD4-deficient mice

The murine γ-herpesvirus 68 replicates in epithelial sites after intranasal challenge, then persists in various cell types, including B lymphocytes. Mice that lack CD4(+) T cells (I-A(b−/−)) control the acute infection, but suffer an ultimately lethal recrudescence of lytic viral replication in the respiratory tract. The consequences of CD4(+) T cell deficiency for the generation and maintenance of murine γ-herpesvirus 68-specific CD8(+) set now have been analyzed by direct staining with viral peptides bound to major histocompatibility complex class I tetramers and by a spectrum of functional assays. Both acutely and during viral reactivation, the CD8(+) T cell responses in the I-A(b−/−) group were no less substantial than in the I-A(b+/+) controls. Indeed, virus-specific CD8(+) T cell numbers were increased in the lymphoid tissue of clinically compromised I-A(b−/−) mice, although relatively few of the potential cytotoxic T lymphocyte effectors were recruited back to the site of pathology in the lung. Thus the viral reactivation that occurs in the absence of CD4(+) T cells was not associated with any exhaustion of the virus-specific cytotoxic T lymphocyte response. It seems that CD8(+) T cells alone are insufficient to maintain long-term control of this persistent γ-herpesvirus.