CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity

We have shown in a murine model system for acute, lethal
cytomegalovirus (CMV) disease in the immunocompromised natural host
that control of virus multiplication in tissues, protection from
virus-caused tissue destruction, and survival are mediated by
virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal
course of disease did not result in a rapid establishment of virus
latency, but led to a long-lasting, persistent state of infection.
The CD8- CD4+ subset of T lymphocytes was not effective by itself
in controlling murine CMV (MCMV) multiplication in tissue or
essential for the protective function of the CD8+ CD4- effector
cells. The antiviral efficacy of the purified CD8+ CD4- subset was
not impaired by preincubation with fibroblasts that presented viral
structural antigens, but was significantly reduced after depletion
of effector cells specific for the nonstructural immediate-early
antigens of MCMV, which are specified by the first among a
multitude of viral genes expressed during MCMV replication in
permissive cells. Thus, MCMV disease provides the first example of
a role for nonstructural herpesvirus immediate-early antigens in
protective immunity.