Interferon Gamma Production by Herpes Simplex Virus Antigen-specific T Cell Clones from Patients with Recurrent Herpes Labialis

Abstract

Nineteen herpes simplex virus (HSV) antigen-specific human T lymphocyte clones were established from three volunteers with recent recurrent herpes labialis. All produced interferon gamma (IFN-γ) at titres of 200 to 700 units/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⁺, Leu 2^-, Leu 3⁺. Interleukin 2 alone failed to induce IFN-γ in titres greater than 10 units/ml from these clones cultured at 10⁴/0.2 ml/well. However, the effect of different accessory or filler cells on IFN-γ production by clones was quite marked. For example, high titres were produced when irradiated PBMC or plastic-adherent cells (predominantly monocytes) were added and low titres 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 titres, but no detectable interferon was produced by the others. However, with higher concentrations of EBV-B cells, low concentrations of IFN-α were occasionally produced. Irradiation strikingly reduced IFN-α production by PBMC. The IFN-α and -γ produced by accessory cells may contribute to total IFN production by priming the production by cloned cells, and acting in synergy with IFN-γ produced by the cloned cells. Alternatively, 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 titres. EBV-B cells from only one of three patients supported antigen-specific lymphocyte activation. Almost all cells of the three 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 two-thirds of the cells of the other two lines.