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Effects Of Ionizing Radiation On Regulatory T Lymphocytes And The Expression Of Related Molecules In Immune Organs In Mice

Posted on:2010-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:F X MengFull Text:PDF
GTID:2144360272996251Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
The mechanisms of radiation immune effects have established a more comprehensive, rigorous and systematic theory, which relates to the overall regulation, cell function, molecular expression, signal transduction, gene regulation and many other fields as well. With the development of immunology, there are much deeper understandings about the immune cells of different subgroups, of which the functions have been revealed continually and the roles in the mechanisms of radiation immune effects remain to be thoroughly investigated.So far the Regulatory T lymphocytes(Treg) are the only discovered negative regulatory function T subset. In our study, a preliminary study on Treg and the related molecules Foxp3 and TGF-β1 exposed to ionizing radiation was carried out in different observation levels including gene, protein and cells to explore the expression of time-and dose-effect changes, further enrich the LDR ionizing hormesis theory, and immune effects of the radiation mechanism of respect of Treg cells to provide a new scientific basis.1. Effects of irradiation on the expression of CD4 and CD25 cells subgroupThe expressions of CD4 and CD25 cells subgroup were detected by flow cytometry. The results in the time-course experiments showed that whether with the low (0.075Gy) or high-dose radiation (2.0Gy), the CD4+CD25+cells in thymus trended to increase. And the thymic CD4+CD25- cells with the low-dose radiation had a significantly increase as well, but no obvious changes when exposed to the high-dose radiation. In the time-course experiments, there were no statistical changes of the thymic CD4+CD25- cells with the low dose radiation, but trended to increase exposed to the high dose radiation. In the dose-effect experiments, the CD4+CD25+cells in thymus had a dose-dependent increase with different dose radiation between 0 and 6Gy. And the thymic CD4+CD25- cells had a dose-dependent increase when exposed to the low dose radiation, but represented a reverse with the high dose radiation. In the dose-effect experiments, the CD4-CD25+ cells in thymus trended to increase both in the status of high or low radiation exposure.In the output of the spleen in time course experiments, both of the low(0.075Gy) and high(2.0Gy) radiation exposure had a increasing level of the CD4+CD25+cells with a peak at the 8th hour time point, then following a slightly decrease but still higher than the sham-irrad globally. And both of the CD4+CD25- and the CD4-CD25+ cells resembled the status in the thymus after the exposure to the high or low dose radiation. In the dose-effect experiments, the CD4+CD25+cells had no significant changes with the low dose radiation, but showed a dose-dependent increase with the high dose exposure. And both of the CD4+CD25- and the CD4-CD25+ cells had a resemblance to the status of the ones in the thymus respectively.2. Effects of irradiation on the expression of Foxp3In the time course experiments about Foxp3 by flow cytometry and RT-PCR, both of the statuses exposed to low or high dose had a peak at the 4th hour time point, following with a gradual decrease back to the sham-irrad level respectively. In the time course experiments, the protein expression level of Foxp3 had no significant changes with the low-dose radiation exposure,but had a time-dependent increase with the high-dose. The Foxp3 mRNA level had a similar status with that of the protein level. In the dose-effect experiments, the mRNA level of Foxp3 exposed to the low dose radiation had no obvious changes, but trended to increase with the high dose radiation. Relatively, both of the thymocytes and the splenocytes had a overall dose-dependent increasing trend in the protein level of Foxp3. 3. Effects of irradiation on the expression of TGF-β1The expressions of TGF-β1 protein were detected by WB and RT-PCR. The results showed that TGF-β1 and Treg cell,both in time-couse and dose-effect for the expression changes, are similar changes, which extent explains the Treg cells in the expression of changing trends with radiation. which confirms the TGF-β1'function on the development and maturity of Treg cells;with high-dose radiation,the promote of TGF-β1 increase in the number of Treg cells, providing conditions for Inhibition of playing.Radiation response results of regulatory T cells suggest that regulatory T cells in the immune effects of radiation to play a certain amount of functions ,and in the mechanisms of low-dose hormesis and high-dose immune suppression regulatory T cells have a role.In summary, different doses of ionizing radiation can enhance the expression of regulatory T cells in the immune organs in mice, in which high-dose radiation-induced the expression of the key elements-Foxp3 and inhibitory factor-TGF-β1 of Treg cells increases.
Keywords/Search Tags:Ionizing radiation, Regulatory T lymphocytes, Foxp3, TGF-β1, Immune response
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