Immune damage in irradiated mice: Contributions of differential radiosensitivity and apoptosis in mononuclear cells, and alterations in natural killer cell cytolytic potential.

摘要

Damage to the immune system of exposed individuals renders the host susceptible to opportunistic infection and disease. The purpose of this investigation was to contribute to the understanding of mechanisms underlying depression of host immune responses following radiation exposure. Peripheral blood mononuclear cells (PBMC) of mice irradiated with 0-700 rad {dollar}gamma{dollar}-whole body irradiation (WBI) were analyzed by flow cytometry (FCA). Natural killer (NK) cells and CD4+ T lymphocytes were selectively enhanced following radiation exposure, demonstrating radioresistance of these cell types over other PBMC, while B lymphocytes were dramatically radiosensitive. Dextran sulfate mobilization of mononuclear cells (MNC) from lymphoid tissues into the blood revealed that the same pattern of MNC loss had occurred throughout the lymphoid tissues. PBMC alterations reflected similar changes occurring in previous studies of splenic mononuclear cells {dollar}{lcub}{dollar}1{dollar}{rcub}{dollar}, and may promote immune dysregulation. The role of apoptosis in radiation-induced injury to the immune system in the low to intermediate dose range (0 to 400 rad) was investigated in PBMC. 25 rad induced apoptosis in PBMC above the unirradiated control within 2 hours post-irradiation; apoptosis induction increased with higher doses (100-400 rad). Additionally, the impact of ionizing radiation on NK cell function was assessed. 24 hours following radiation exposure, NK cytotoxicity against YAC-1 target cells was depressed by doses of 25 or 50 rad, with little change in the 100 to 400 rad range. By day 7, NK cytolytic potential was reduced or unaffected by doses lower than 200 rad, while a single exposure of 400 rad enhanced cytotoxicity. The results of this investigation have furthered our understanding of factors which may be important in the impairment of immune responses post-irradiation.