| Background:Autoimmune regulator as a transcript factor was firstly cloned in 1997. The mutant of AIRE can lead to the APECED in human beings. AIRE is highly expressed on medulla thymic epithelial cells (mTECs). At the same time, mTECs can express various tissue restricted antigens (TRAs). It has been confirmed that AIRE play an important role in central immune tolerance by controlling these TRAs. That is it will help to eliminate the autoreactive T cell and prevent from autoimmune diseases through the negtive selection. In addition, AIRE are expressed on many peripheral immune organs, such as spleen and lymph nodes. And the expressing of AIRE has been detected on several types of cells, dendritic cells, epithelial cells and fibroblast recticular cells and so on. However, the functions of AIRE expressed on these cells are still not known, which prompts us to explore.Regulatory T cell (Treg) is an immportant population in maintaining immune tolerance. These cells are derived from thymus and play their functions in peripheral tissues. Many kinds of diseases will occur with abnormal number or function of these cells. It had been reported that CD4+ Treg play a key role in supressing autoimmune, inducing graft tolerance, tumor, resisting infection, pregnancy and hypersensitivity. So far, Foxp3 as a transcript factor was considered a most specific marker for these cells, and Foxp3 plays a crucial role in development and function of these cells. Wheras, Makoto Miyara reported that it is not a homogeneous population, and can be divided into three subsets, including CD4+CD45RA+Foxp3loTreg (resting Treg cells, rTreg), CD4+CD45RA-Foxp3hiTreg (activated Treg cells, aTreg) and CD4+CD45RA-Foxp3loTreg (non-Treg). rTreg are a resting cells in normal condion while aTreg appear after activation. Both of them are the suppressive T cells. But non-Treg are more similar to effective T cells although expressing Foxp3 also, and this subset has the ability to secret IL-17.Therfore, it suggests there are some relations between AIRE and Treg probably. But which subsets of Treg will be related to AIRE?Objective:To explore the relationship between AIRE and Treg in peripheral immune system.Method:AIRE transfected RAW264.7 cells (mouse macrophage) or their supernanant were cocultured with mice spleenocytes, the percentage of CD4+Foxp3+T cells or their subsets were dectected by FACS. 1. When RAW264.7 cells expressing AIRE was cocultured with mice spleenocytes directly, the number of CD4+Foxp3+T cells increased at 72h but no difference at 48h. rTreg decreased at 48 and increased significantly at 72h. aTreg and non-Treg showed continuously reduce.2. When the supernanant of RAW264.7 cells expressing AIRE was cocultured with mice spleenocytes, the number of CD4+Foxp3+T changed unobviously. But the number of aTreg was increased. There were no change with rTreg and non-Treg.Conclusion:1. AIRE may promote the production of rTreg by the direct cell-cell contact as well as reduce non-Treg to maintain the tolerance.2. AIRE can also in directly induce the increase of aTreg by inducing certain substance screcting by the cells to suppress the immune response and prevent from autoimmune diseases.In this study, the effects of AIRE on CD4+Foxp3+T cells and their subsets were investigated. AIRE may control different subsets of Treg by direct or indirect pathway respectively. It will provide the evidence to better understand the mechanism of APECED, and new ideas for diagnosing or treating the autoimmune diseases by artifically manipulating AIRE and CD4+Foxp3+T cells. |
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