Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Luo-Owen, X., Pecaut, M. J., Rizvi, A. and Gridley, D. S. Low-Dose Total-Body gamma Irradiation Modulates Immune Response to Acute Proton Radiation. Radiat. Res. 177, 251-264 (2012). Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate gamma rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with Co-57 (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to gamma rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to gamma rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3(+) T, CD19(+) B, CD4(+) T, CD8(+) T and NK1.1(+) natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with gamma radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate gamma rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations. (C) 2012 by Radiation Research Society