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Peripheral Mature T Cells’ Migration Into Thymus And Its’ Function In Normal Mice

Posted on:2018-03-27Degree:MasterType:Thesis
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:2334330512982495Subject:Biological engineering
Abstract/Summary:PDF Full Text Request
In the study of the function of the thymus,the thymus has been identified as an immune privileged organ.This means that antigens and macromolecules can not enter into the thymus.Therefore,immune response is avoided,in other words,antigens getting into thymus will be tolerated.According to the central tolerance mechanism theory,if non-self antigen is transferred into thymus,it will be recognized by the developing T lymphocytes.This will leave bad influence on the positive selection and cathodic selection,even make the antigen-specific T cells apoptosis.Controversially,our previous work did not induce the tolerance to tumor after we inject tumor cells into the thymus.These cells were cleared eventually.Further more,flow analysis showed that the proportion of single positive cells in the thymus increased after injecting tumor cells.So we raised a question that apart from differentiating from the double-positive cells,are these increased single-positive cells derived from the peripheral mature T cells?In experiments with transplanted T cells in immunodeficient mice,researcher found that allogeneic mature T cells could enter the thymus.But it is uncertain whether the peripheral mature T cells of normal mice also have this ability of reentering into the thymus.Therefore,in view of the above problems,we use normal mice as the experimental objects.In order to explore whether there are mature T cells from the periphery in the thymus,we,first injected CFDA SE fluorescent dyes into the spleens of normal mice,and then analyze whether the thymus contained cells expressing CFDA SE fluorescence signal by FCM.To further explore the immune response in the thymus,Secondly,we injected the same amount of A549 cells into the thymus of mice immunized with A549 cell antigen and nonimmunized mice.The paraffin sections and flow cytometry were used to analyze the immune responses,the state of the antigenic cells and the changes of T cell subsets in the thymus.We get the following results through the above experiment:1.We can detect CFDA SE positive cells,and the vast majority of these cells were CD3 positive.2.The result of paraffin section showed that the immune response occurred in the thymus of the immunized mice was more severe than that of the nonimmunized mice,and the thymus could return to normal in a relatively shorter time.3.The results of FCM showed that the survival time of A549 cells in the thymus of the immunized mice was shorter than that of the nonimmunized mice.4.Compared with those mice without thymic injection,the number of CD4+,CD8+single-positive T cells in the thymus was significantly increased in immunized and nonimmunized mice at day 5 after thymic injection.The ratio of CD8 +/CD4 + in the immunized mice’ thymus was significantly higher than that in the nonimmunized mice,but there was no significant difference between the nonimmunized mice and the mice without thymus injection.Through the above results,we draw the following conclusions:1.The peripheral mature T cells can enter into the thymus of normal mice.It is a kind of phenomenon that not only occurred in immunodeficient mice,but also occurred in normal mice.2.When the same antigen enter into the thymus after immunization,there will be more timely and violent immune response.Based on the above conclusions,we speculate that part of the memory T cells could get into the thymus after peripheral immunity.When these cells encounter the corresponding antigen again in thymus,they would proliferate rapidly and damage the antigens.It may be a normal mechanism that protecting the thymus from antigen infection by peripheral mature T cells returned to the thymus to prevent the formation of the tolerance to foreign antigens.
Keywords/Search Tags:thymus, T lymphocytes, A549, tolerance, immune memory
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