Low-dose gamma-rays modify CD4(+) T cell signalling response to simulated solar particle event protons in a mouse model

Purpose: Astronauts on missions are exposed to low-dose/low-dose-rate (LDR) radiation and could receive high doses during solar particle events (SPE). This study investigated T cell function in response to LDR radiation and simulated SPE (sSPE) protons, alone and in combination. Materials and methods: C57BL/6 mice received LDR gamma-radiation (Co-57) to a total dose of 0.01 Gray (Gy) at 0.179 mGy/h, either with or without subsequent exposure to 1.7 Gy sSPE protons delivered over 36 h. Mice were euthanised on days 4 and 21 post-exposure. T cells with cluster of differentiation 4 (CD4(+)) were negatively isolated from spleens and activated with anti-CD3 antibody. Cells and supernatants were evaluated for survival/signalling proteins and cytokines. Results: The most striking effects were noted on day 21. In the survival pathway, nuclear factor-kappaB (NF-kappa B; total and active forms) and p38 mitogen activated protein kinase (p38MAPK; total) were significantly increased and cJun N-terminal kinase (JNK; total and active) was decreased when mice were primed with LDR gamma-rays prior to sSPE exposure (P < 0.001). Evaluation of the T cell antigen receptor (TCR) signalling pathway revealed that LDR gamma-ray exposure normalised the high sSPE proton-induced level of lymphocyte specific protein tyrosine kinase (Lck; total and active) on day 21 ( < 0.001 for sSPE vs. LDR + sSPE), while radiation had no effect on active zeta-chain-associated protein kinase 70 (Zap-70). There was increased production of interleukin-2 (IL-2) and IL-4 and decreased transforming growth factor-beta 1 in the LDR + sSPE group compared to the sSPE group. Conclusion: The data demonstrate, for the first time, that protracted exposure to LDR gamma-rays can significantly modify the effects of sSPE protons on critical survival/signalling proteins and immunomodulatory cytokines produced by CD4(+) T cells.