HERPES-SIMPLEX VIRUS-SPECIFIC HUMAN CYTOTOXIC T-CELL COLONIES EXPRESSING EITHER GAMMA-DELTA OR ALPHA-BETA-T-CELL RECEPTOR - ROLE OF ACCESSORY MOLECULES ON HLA-UNRESTRICTED KILLING OF VIRUS-INFECTED TARGETS

Previous studies have demonstrated that herpes simplex virus-1 (HSV-1) -infected mononuclear cells are able to stimulate autologous periphera l blood mononuclear cells (PBMC) of immune donors and to activate HSV- specific cytotoxic T lymphocytes (CTL) expressing either gamma delta o r alpha beta T-cell receptors (TCR). In the present report characteriz ation of 10 gamma delta(+) and six alpha beta(+) HSV-specific cytotoxi c T-cell colonies (TCC) is described. Cytotoxic colonies were derived from HSV-induced cell fines of three donors who, in previous experimen ts, had shown a prevalence of gamma delta(+) or alpha beta(+) effector cells. HSV-1 induced cell lines obtained from gamma delta responders included more than 80% of cells expressing V gamma 9/delta 2 TCR V reg ion chains. gamma delta(+) TCC also expressed V gamma 9/delta 2 molecu les. alpha beta(+) TCC all expressed CD8 antigen, while only one of 10 gamma delta(+) TCC was CD8(+), the others being CD4/CD8-double negati ve. The cytotoxic response of HSV-specific TCC was HLA-unrestricted; n evertheless CD8(+) TCC were dependent on the expression of HLA class I on the, surface of target cells to mediate cytolytic activity, while CD8(-) TCC were not. Blocking experiments with monoclonal antibody (mA b) specific for lymphocyte function-associated antigen-1 (LFA-1), whic h is expressed. on all TCC, demonstrated that all alpha beta(+) TCC an d some gamma delta(+) TCC also needed the interaction between LFA-1 an d its ligands to develop cytotoxic activity. Altogether our data sugge st that HSV-specific CTL may represent a population selected by a high concentration of antigen with a broad range of TCR affinities, which may play an important role as a first line of defence against infectio n.