Low-dose, low-dose-rate proton radiation modulates CD4(+) T cell gene expression

Area of Science:

• Spaceflight radiation biology
• Immunology
• Molecular biology

Background:

• Spaceflight exposes astronauts to proton radiation, a significant health concern.
• Understanding the effects of this radiation on the immune system, particularly T cells, is crucial for astronaut safety.

Purpose of the Study:

• To investigate changes in gene expression and related parameters of CD4(+) T cells following whole-body proton radiation exposure.
• To assess the impact of varying low doses of proton radiation, simulating spaceflight conditions, on immune cell function.

Main Methods:

• C57BL/6 mice were exposed to whole-body proton radiation at doses of 0, 0.01, 0.05, and 0.1 gray (Gy).
• CD4(+) T cells were isolated from spleens, and the expression of 84 T helper cell-related genes was analyzed using RT-PCR.
• Cell counts, CD4:CD8 ratios, and spontaneous DNA synthesis were measured at various time points post-irradiation.

Main Results:

• Low-dose proton radiation (0.01 Gy and 0.1 Gy) significantly altered the expression of genes related to T helper cell function.
• At 0.01 Gy, five genes were upregulated and three were downregulated; at 0.1 Gy, nine genes were upregulated and none were downregulated.
• A dose of 0.01 Gy led to reduced CD4(+) T cell counts and CD4:CD8 ratios in the spleen and decreased spontaneous DNA synthesis.

Conclusions:

• Protracted low-dose proton irradiation significantly modifies CD4(+) T cell gene expression in a dose-dependent manner.
• Low-dose proton radiation, particularly 0.01 Gy, may enhance CD4(+) T cell responsiveness, suggesting complex immune modulation.
• These findings are critical for understanding the immunological risks associated with long-duration space missions.