INTERFERON-GAMMA PRODUCTION BY HERPES-SIMPLEX VIRUS ANTIGEN-SPECIFIC T-CELL CLONES FROM PATIENTS WITH RECURRENT HERPES LABIALIS

Nineteen herpes simplex virus (HSV) antigen-specific human T lymphocyte clones were established from 3 volunteers with recent recurrent herpes labialis. All produced interferon gamma (IFN-.gamma.) at titers of 200-700 U/ml when cultured in vitro with HSV antigen and irradiated peripheral blood mononuclear cells (PBMC) as filler cells. All 10 of those clones whose phenotype was determined were Leu 4+, Leu2-, Leu3+. Interleukin 2 alone failed to induce IFN-.gamma. in titers greater than 10 U/ml from these clones cultured at 104/0.2 ml per well. The effect of different accessory or filler cells on IFN-.gamma. production by clones was quite marked. For example, high titers were produced when irradiated PBMC or plastic-adherent cells (predominantly monocytes) were added and low titers when macrophages and irradiated Epstein-Barr virus-transformed B (EBV-B) cells were added. When tested for HSV antigen-stimulated IFN production alone, the irradiated PBMC and adherent cells produced low titers, but no detectable interferon was produced by the others. With higher concentrations of EBV-B cells, low concentrations of IFN-.alpha. were occasionally produced. Irradiation strikingly reduced IFN-.alpha. production by PBMC. The IFN-.alpha. and -.gamma. produced by accessory cells may contribute to total IFN production by priming the production by cloned cells, and acting in synergy with IFN-.gamma. produced by the cloned cells. The effect may be due to the presence of permissive concentrations of other lymphokines such as the interleukins. Interferon production by cloned T lymphocytes in the presence of non-producing macrophages was maximal within 24 h, much faster than with a similar polyclonal system, although attaining lower titers. EBV-B cells from only 1 of 3 patients supported antigen-specific lymphocyte activation. Almost all cells of the 3 cell lines expressed DR antigens, while DS/DC antigens were also expressed on nearly all cells of the antigen-presenting line and, at lower densities, on 2/3 of the cells of the other 2 lines.