Abstract
BackgroundThe present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation.ResultsThe stimulatory effect of low dose radiation (LDR) on the proliferative response of lymphocytes to Con A was found to require the presence of APCs. The addition of APCs obtained from both low- and high-dose-irradiated mice to splenic lymphocytes separated from low-dose-irradiated mice caused stimulation of lymphocyte proliferation. B7-1/2 expression on APCs was up-regulated after both low and high doses of radiation. There was up-regulation of CD28 expression on splenic and thymic lymphocytes after LDR and its suppression after high dose radiation (HDR), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression showed changes in the opposite direction. IL-12 secretion by macrophages was stimulated after both low and high doses of radiation, but IL-10 synthesis by splenocytes was suppressed by low dose radiation and up-regulated by high dose radiation.ConclusionThe status of CD28/CTLA-4 expression on T lymphocytes in the presence of up-regulated B7 expression on APCs determined the outcome of the immune changes in response to radiation, i.e., up-regulation of CD28 after LDR resulted in immunoenhancement, and up-regulation of CTLA-4 associated with down-regulation of CD28 after HDR led to immunosuppression. Both low and high doses of radiation up-regulated B7-1/2 expression on APCs. After LDR, the stimulated proliferative effect of increased IL-12 secretion by APCs, reinforced by the suppressed secretion of IL-10, further strengthened the intracellular signaling induced by B7-CD28 interaction.
Highlights
The present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation
As illustrated in Group A of figure 1, the proliferation of splenocytes in response to Con A after whole-body irradiation (WBI) with 0.075 Gy was significantly up-regulated to a value more than doubling that of the sham-irradiated control (P < 0.002, A1 vs A2), while WBI with 2 Gy caused a profound depression of this reaction to about one third of the control (P < 0.01, A1 vs A3)
When antigen-presenting cells (APCs) from both the 0.075Gy-irradiated and 2Gy-irradiated mice were added to the separated lymphocytes, the proliferative response of lymphocytes from the control mice recovered (P > 0.05, A1 vs Dl and A1 vs E1) and that of lymphocytes from the 0.075 Gy-irradiated mice was greater than the control of each group (P < 0.02, D1 vs D2; P < 0.05, E1 vs E2), and this response was greater than the normal control (P < 0.05, A1 vs D2 and A1 vs E2)
Summary
The present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation. BMC Immunology 2001, 2:8 http://www.biomedcentral.com/1471-2172/2/8 mental low level radiation [2,3,4,5,6,7] This is the reason why the studies on the mechanisms of the stimulatory effect of LDR have attracted the attention of radiobiologists and health physics workers. In the present paper it is demonstrated for the first time that the cellular interactions between the APCs and lymphocytes play an important role in the distinct changes in the immune response following exposure of mice to different doses of radiation with possible involvement of the costimulatory factors and cytokines in such changes
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