T-cell-mediated cytotoxicity against herpes simplex virus-infected target cells

Abstract

THE control of herpes simplex virus (HSV) infection by immunological mechanisms seems to be complex and is poorly understood. Neutralising antibodies to HSV plus complement seem to have no effect on the propagation of HSV infection, because HSV spreads to adjacent cells by passing through intercellular bridges1–3. Anti-HSV antibodies plus complement, however, destroy virus-infected cells, but cannot prevent the spread of HSV, suggesting that the virus must be transferred to neighbouring cells before immune lysis occurs1,5. Therefore if lymphocyte-mediated cytolytic mechanisms are instrumental in blocking the spread of HSV in vivo, they ought to destroy infected cells at a very early stage in the viral maturation cycle, before infectious viral particles are produced. Indeed, effective antibody dependent cell-mediated cytotoxicity (ADCC) has been demonstrated in vitro using target cells infected with HSV4,5. In this system K-cell-mediated destruction of virus-infected cells takes place very early in the infectious cycle5. As in vivo protection against HSV infection is predominantly T-cell-dependent6,7, the in vivo spread of HSV infections may be controlled by virus-specific cytotoxic T lymphocytes (CTL). But no virus-specific CTL so far have been detected in the spleen of HSV-infected mice. Using a different experimental approach we have now shown that T lymphocytes of mice undergoing a local HSV infection, when transferred in vitro, differentiate into effective CTL. The CTL generated are highly cytotoxic for HSV-infected target cells.