Low-dose photon and simulated solar particle event proton effects on Foxp3+ T regulatory cells and other leukocytes.
Radiation is a major factor in the spaceflight environment that has carcinogenic potential. Astronauts on missions are continuously exposed to low-dose/low-dose-rate (LDR) radiation and may receive relatively high doses during a solar particle event (SPE) that consists primarily of protons. However, there are very few reports in which LDR photons were combined with protons. In this study, C57BL/6 mice were exposed to 1.7 Gy simulated SPE (sSPE) protons over 36 h, both with and without pre-exposure to 0.01 Gray (Gy) LDR g-rays at 0.018 cGy/h. Apoptosis in skin samples was determined by immunohistochemistry immediately post-irradiation (day 0). Spleen mass relative to body mass, white blood cells (WBC), major leukocyte populations, lymphocyte subsets (T, Th, Tc, B, NK), and CD4(+)CD25(+)Foxp3+ T regulatory (Treg) cells were analyzed on days 4 and 21. Apoptosis in skin samples was evident in all irradiated groups; the LDR+sSPE mice had the greatest expression of activated caspase-3. On day 4 post-irradiation, the sSPE and LDR+sSPE groups had significantly lower WBC counts in blood and spleen compared to non-irradiated controls (p < 0.05 vs. 0 Gy). CD4(+)CD25(+)Foxp3(+) Treg cell numbers in spleen were decreased at day 4, but proportions were increased in the sSPE and LDR+sSPE groups (p < 0.05 vs. 0 Gy). By day 21, lymphocyte counts were still low in blood from the LDR+sSPE mice, especially due to reductions in B, NK, and CD8(+) T cytotoxic cells. The data demonstrate, for the first time, that pre-exposure to LDR photons did not protect against the adverse effects of radiation mimicking a large solar storm. The increased proportion of immunosuppressive CD4+CD25(+) Foxp3(+) Treg and persistent reduction in circulating lymphocytes may adversely impact immune defenses that include removal of sub-lethally damaged cells with carcinogenic potential, at least for a period of time post-irradiation.
Department of Radiation Medicine, University and Medical Center, Loma Linda, CA 92354, USA. dgridley@dominion.llumc.edu
Daila S
DS
Gridley
Xian
X
Luo-Owen
Asma
A
Rizvi
Adeola  Y
A
Makinde
Michael  J
M
Pecaut
Xiao W
XW
Mao
James M
JM
Slater
D000818:Animals; D001835:Body Weight / Q000528:radiation effects; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017785:Photons / Q000009:adverse effects*; D011522:Protons / Q000009:adverse effects*; D011829:Radiation Dosage; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D019445:Solar Activity; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000528:radiation effects*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011522:Protons