Induction of Tumor Necrosis Factor α Expression in Human T Lymphocytes Following Ionizing Gamma Irradiation

Abstract

In this work, we present evidence that enriched human peripheral blood T lymphocytes, depleted of contaminating monocytes, rapidly express tumor necrosis factor α (TNF-α) mRNA when exposed to low doses of γ-irradiation. In total PBL, TNF-α mRNA accumulation increased threefold as early as 30 minutes following exposure to 4 Gy and then declined to the baseline level by 3-5 h, as measured by the reverse transcriptase-polymerase chain reaction (RT-PCR). The increase in TNF-α mRNA was also observed in populations of enriched T cells and decreased when the dose of irradiation was increased to 10 Gy, strongly suggesting that T lymphocytes, the most radiosensitive cells of the body, contributed directly to the increase of TNF-α mRNA. A good correlation was found between mRNA expression and TNF-α protein secretion. Interestingly, a eightfold increase in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA accumulation was also detected in both PBL and enriched T cells irradiated at 4 Gy for 3 h compared with unirradiated cells. This irradiation effect was almost completely abolished, however, following exposure to 10 Gy. Together these data suggest that T cells are responsible for the irradiation-induced expression of TNF-α and GAPDH.