Radiosensitivity of isolated subsets of human lymphocytes (E+, OKT4+, OKT8+): protective role of monocytes and monokines.
The sensitivity of human peripheral blood T lymphoid populations to 60Co ionizing radiation was investigated. Dose-response values were determined for populations that are commonly identified by their ability to form spontaneous rosettes with sheep red blood cells (E+ cells), helper T lymphocytes (OKT4+ cells) and suppressor T lymphocytes (OKT8+ cells). OKT4+ and OKT8+ T cell subsets were negatively selected by complement (C)-mediated cytolysis using the C fixing OKT4 and OKT8 monoclonal antibodies (MoAb). The irradiation-induced damage was assessed by the lymphoblast transformation test, using the polyclonal T cell mitogen, phytohaemagglutinin (PHA) and the OKT3 MoAb. (The OKT3 antibodies are mitogenic for T cells only in the presence of monocytes). No significant differences were evident between dose-response values of E+, OKT4+ and OKT8+ lymphoid subpopulations when using PHA as a mitogen. On the other hand, when OKT3 was used to trigger resting irradiated peripheral blood T lymphocytes, e.g. E+ cells, OKT3 stimulated T cells proved to be markedly radioresistant as compared to PHA stimulated cell cultures. This was found to result from the fact that purified T cell cultures were co-cultured with non-irradiated monocytes when OKT3 was employed as a motogen. Similarly co-culturing of irradiated E+, OKT4+ and OKT8+ cells with non-irradiated autologus monocytes partially corrected the irradiation damage, regardless of the mitogen employed. More important, however, was the observation that macrophage derived supernatants containing (interleukin-1) IL-1 could confer a high degree of radioprotection on irradiated E+ cells. It is concluded that monocytes and monocyte products partially protect against irradiation damage.