The purpose of this study was to determine whether the enhanced proliferative activity of splenocytes induced by exposing mice to whole body, chronic, intermittent low doses of ionizing radiation is associated with an increase in the expression of stress protein genes. Mice were exposed to a gamma-irradiation protocol of 0, 0.04 or 0.10 Gy/day for 5 consequent days/week, for 4 weeks. Splenocytes were then assessed for their levels of heat shock protein (HSP) 70 mRNA, glyceraldehyde 3-phosphate dehydrogenase (GAPD) mRNA, HSC70 (a constitutively-expressed isoform of HSP70) and HSP72 (an inducible isoform of HSP70), before and 1 day after mitogenic stimulation. Splenocytes from mice exposed to 0.04 Gy/exposure contained elevated constitutive levels of HSP70 mRNA, HSC70 and HSP72. These splenocytes responded to T, but not B, cell mitogens by further increasing their levels of HSP70 mRNA, HSC70 and HSP72 and by mounting a heightened proliferative response. However, an exposure of 0.10 Gy was ineffective. Thus, the constitutive levels of HSP70 mRNA, HSC70 and HSP72 and the mitogen-stimulated levels of HSC70 and HSP72 of splenocytes from mice exposed to 0.10 Gy/exposure were comparable with those of sham-irradiated mice. Moreover, their proliferative activity in response to mitogenic stimulation was also comparable with that of splenocytes from sham-irradiated mice.
The proliferative response to mitogenic stimulation by splenocytes can be augmented by exposing mice to whole-body, chronic, intermittent low doses of ionizing radiation, referred to here as low-dose irradiation. The purpose of this study was to identify the cell(s) in the spleen which is responsive to the proliferation-augmenting effect of low-dose irradiation, i.e., the cellular target. C57BL/6 mice were subjected to low-dose irradiation (0.04 Gy/exposure/day, 5 consecutive days/week, 2 weeks) or to sham irradiation. Three days after the last exposure, spleens were removed, separated into cell fractions which were nonadherent and adherent to plastic surfaces and reconstituted in various combinations, and their proliferative responses to various mitogens were determined. Highly purified T cells were also used in place of the nonadherent cell fraction in the reconstitution studies. The target cells were shown to be T cells. The target T cells of low-dose-irradiated mice possessed elevated constitutive levels of HSP-70 mRNA and HSP-72, and they responded to T-cell receptor-specific anti-CD3 stimulation by producing more HSP-70 mRNA and HSP-72 and by proliferating more extensively than T cells of sham-irradiated mice.
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