Cytotoxic T lymphocytes. Their relevance in herpesvirus infections.

We have used recombinant vaccinia viruses expressing the cloned genes coding for glycoprotein B (gB) or glycoprotein D (gD) of HSV-1 to analyze the role of HSV-1--specific cytotoxic T lymphocytes (CTL) in antiviral immunity. Various studies in mice revealed that either vector could stimulate some aspects of HSV-1--specific immunity, but surprisingly, HSV-specific CTL were not induced. Even though gD appeared to be a target antigen for class II-MHC-restricted CTL, neither the gB or the gD vector was capable of forming a target-cell complex that was recognized by class I-MHC-restricted HSV-specific CTL. The inability of these major extracellular glycoproteins to act as CTL-target antigens was even more unusual in light of the ability of CTL to apparently recognize the immediate early genes of HSV, none of which are considered to be expressed on the surface of infected cells. The selective failure of either the gB or gD vector to induce numerous aspect of anti-HSV immunity in the absence of a CTL response allowed us to assess the consequence of this failure in terms of the level of protective immunity against HSV challenge seen in vector-immunized mice. These studies suggest that this failure to induce HSV-specific CTL appears to minimize the protective response to only efficiently protecting against low-challenge doses of HSV-1. These findings are discussed with relevance to the role of CTL in the control of herpesvirus infections.