ROLE OF T-CELLS IN ANTI-HERPES SIMPLEX VIRUS IMMUNITY .1. INDUCTION OF ANTIGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

Abstract

Mice infected with herpes simplex virus [HSV] develop little or no cytotoxic T [thymus derived] lymphocyte (CTL) response. In lymph nodes draining a local site infected with HSV, antigen-specific CTL precursors are sensitized, which upon transfer to in vitro culture conditions develop within 72 h into effective CTL. The in vivo blockage of CTL differentiation can be overcome by cyclophosphamide, suggesting that a cyclophosphamide-sensitive mechanism blocks the in vivo generation of HSV-immune CTL. The cytolytic activity of HSV-immune CTL is H-2 restricted and antigen specific. Thus CTL sensitized toward HSB type 1 discriminate between syngeneic targets infected with the immunologic HSV variatn type 1 or type 2 (and vice versa). H-2-matched target cells exposed for 30 min to infectious HSV are lysed within 60 min of contact with CTL. Since HSV replication requires more than 4-5 h, either the expression of HSV-dependent early proteins takes place within 30-90 min or cell membrane-integrates HSV virion represents the target antigen of CTL.