Low-dose, low-dose-rate proton radiation modulates CD4(+) T cell gene expression.
OBJECTIVE
To evaluate cluster of differentiation 4(+) (CD4(+)) T cell gene expression and related parameters after whole-body exposure to proton radiation as it occurs in the spaceflight environment.


METHODS
C57BL/6 mice were irradiated to total doses of 0, 0.01, 0.05, and 0.1 gray (Gy) at 0.1 cGy/h. On day 0 spleens were harvested from a subset in the 0, 0.01 and 0.1 Gy groups; (CD4(+)) T cells were isolated; and expression of 84 genes relevant to T helper (Th) cell function was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). Remaining mice were euthanized on days 0, 4, and 21 for additional analyses.


RESULTS
Genes with >2-fold difference and p < 0.05 compared to 0 Gy were noted. After 0.01 Gy, five genes were up-regulated (Ccr5, Cd40, Cebpb, Igsf6, Tnfsf4) and three were down-regulated (Il4ra, Mapk8, Nfkb1). After 0.1 Gy there were nine up-regulated genes (Ccr4, Cd40, Cebpb, Cxcr3, Socs5, Stat4, Tbx21, Tnfrsf4, Tnfsf4); none were down-regulated. On day 0 after 0.01 Gy, CD4(+) T cell counts and CD4:CD8 ratio were low in the spleen (p < 0.05). Spontaneous DNA synthesis in both spleen and blood was lowest in the 0.01 Gy group on day 0; on days 4 and 21 all p values were >0.1.


CONCLUSIONS
The data show that the pattern of gene expression in CD4(+) T cells after protracted low-dose proton irradiation was significantly modified and highly dependent upon total dose. The findings also suggest that low-dose radiation, especially 0.01 Gy, may enhance CD4(+) T cell responsiveness.
Gridley
Daila S
DS
Department of Radiation Medicine, Radiation Research Laboratories, Loma Linda University, CA 92354, USA. dgridley@dominion.llumc.edu
Pecaut
Michael J
MJ
Rizvi
Asma
A
Coutrakon
George B
GB
Luo-Owen
Xian
X
Makinde
Adeola Y
AY
Slater
James M
JM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000096:biosynthesis / Q000097:blood; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D011522:Protons; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
D011522:Protons; D004247:DNA