Study On The Expression And Function Of CD4+CD25-Foxp3+ Cells In Uygur And Han SLE Patients

Objective:In recent years,many medical reports and scientific research results have had in-depth research on the systemic lupus erythematosus(SLE)disease state,the number and function of regulatory T cells(Treg cells),but differences are found in the results of different research groups.Decrease,unchangedness and increase in the proportion of Treg cells in peripheral blood have all been reported,and the decrease and unchangedness in the immunosuppressive function of Treg cells as well.The differences in the above findings may be related to racial differences in patients,disease progression,selected treatments,and the classification of surface molecular markers when the investigator defines Treg.In this study,patients with newly diagnosed SLE of different ethnic groups were tested for CD4+CD25-Foxp3+,a group of T cells with unclear nature;the expressions of these cells in healthy people,SLE patients and in Uygur and Han nationalities,and their relevance to the disease were observed;further clarification of the nature and function in their proliferation and secretion of cytokines by in-vitro culture has been made.This study has meant to provide necessary theoretical supplements for the possible pathogenesis of SLE,as well as some theoretical basis for targeted therapy for re-establishing immune tolerance in SLE in the future.Methods:This study selected 38 patients with initial SLE(untreated yet)in the dermatology clinic and wards of the People's Hospital of Xinjiang Autonomous Region from April 2013 to September 2015.Among them,18 patients were Uygur and 25 patients Han.The healthy control group selected 20 cases respectively from Uygur and Han nationalities who received physical examination during the same period at the People's Hospital of Xinjiang Autonomous Region.They participated in the study voluntarily.The basic variables such as gender and age were matched,and there was no recent history of infection,long-term non-immune disease or tumor history found.Peripheral blood mononuclear cells(PBMC)were isolated by sterile,CFSE staining and stimulation of proliferation culture,cell separation and functional analysis.Results:1)Uygur people were more susceptible to light sensitivity and hair loss as the first symptom than Han SLE.2)The percentage of CD4+CD25-Foxp3+T cells in peripheral blood of Uygur and Han people increased.3)There was no difference in the expression of CD4+CD25-Foxp3+T cells between Uygur and Han.4)In both Uygur and Han people,the expression of CD27+cells in CD4+CD25-Foxp3+T cells in active SLE patients were significantly lower than those in inactive SLE patients and HC.5)In both Uygur and Han people,in CD4+CD25-Foxp3+T cells,the expression of CCR6 in the active group was significantly higher than that in the healthy control group.6)The expression of conventional markers CD4+CD25-Foxp3+T cells decreased in Uygur and Han people.7)After 72 hours of anti-CD3 stimulation,CD4+CD25+T cells showed significant proliferative responses in either the Uygur and Han healthy control or the activity group SLE,whereas CD4+CD25-Foxp3+T cells had no proliferative response.8)CD4+CD25+CD127-in patients with SLE active group could inhibit the anti-CD3 induced proliferation of the effect or T cell population,and the CD4+CD25-CD127-T cell population had the same inhibitory ability.9)In both Uygur and Han SLE,IFN-? production was significantly inhibited in co-culture of CD4+CD25+CD127-T cells with effect or T cells,whereas CD4+CD25-CD127-T cells did not inhibit IFN-? production.Conclusion:CD4+CD25+Foxp3+Treg,which specifically inhibit immune response,may be closely related to the pathogenesis of autoimmune diseases.Studies have described an increase in the proportion of CD4+Foxp3+T cells lacking CD25 expression in SLE patients,but the inhibition ability of these cells has not been analyzed so far.In this study,we performed a combined phenotypic and functional analysis of CD4+CD25-Foxp3+T cells in Uygur and Han SLE patients and healthy controls(HC).Phenotypic analysis showed that the proportion of CD4+CD25-Foxp3+T cells increased in both SV and SLE patients.According to phenotypic analysis,CD4+CD25-Foxp3+T cells were similar to Treg but not activated T cells.For functional analysis,a surrogate surface marker combination replacing intracellular Foxp3 was defined: CD4+CD25-CD127-T cells from SLE patients were isolated by FACS sorting and analyzed for their ability to inhibit in vitro.CD4+CD25-CD127-T cells containing Foxp3+T cells were found to inhibit T cell proliferation but did not inhibit IFN-? production in vitro.In conclusion,CD4+CD25-Foxp3+T cells are also functionally similar to conventional Tregs in phenotype and to some extent.Despite the increased proportion,its selective functional defects can cause Tregs to go out of control in order to achieve effective control of immune disorders in SLE patients.In addition,there was no significant difference found in the expression frequency and functional characteristics of CD4+CD25-Foxp3+T cells between Uygur and Han.