Low Dose IL-2 Restores Imbalance Between TH17 And Regulatory T Cells In Patients With Connective Tissue Disease Combined With EBV/CMV Viremia

Background:For a long time,disease-modifying antirheumatic drugs(DMARDs)are the most important medicine in treatment of autoimmune disease.However,excessive using DMARDs lead to decrease immune function,which increasing opportunistic infection,such as EBV,CMV viremia.Recent study show that the imbalance between T help cell 17(Th17)and regulatory T cell(Treg cell)is a pivotal cause of autoimmune disease and correction of this imbalance to be a potential therapy.Whether low dose IL-2 restores the balance of Th17/Treg and improve immune function? In this study,we will investigate the effect of low-dose recombinant human IL-2(rh IL-2)on Treg and effector lymphocytes cell subsets in patients with connective tissue disease(CTD)combined EBV and CMV viremia.Objectives:To investigate the effect of low-dose IL-2 on Tregs and effector lymphocytes cell subsets in patients with CTD combined EBV and CMV viremia.Methods:Clinical records of 70 CTD patients combined EBV and CMV viremia(Group infection),hospitalized from May 2012 to January 2017 in Shan Xi medical university the second Hospital,were analyzed.Of the 70 patients,18 were males,and 50 females.Their age was(50±35).And they all had glucocorticoid and traditional DMARDs medication.As control,we selected 70 health persons(Group health)whose age matched with group infection,70 na?ve CTD patients with no treatment(Group treatment-na?ve),and 70 CTD without viremia patients having glucocorticoid and DMARDS medical history(Group Treatment-DMARDS).The two groups are both matched with group infection by underlying diseases.The absolute numbers and proportions of Tregs and effector lymphocytes cell subsets in peripheral blood were examined by flow cytometry.1.Treg cells and effector lymphocytes subsets were analyzed by comparing in Group health and Group treatment-na?ve,Group treatment-na?ve and Group treatment-DMARDS,Group treatment-DMARDS and Group infection.2.Statistical analyses were conducted with SPSS22.0 software.3.Group infection include 21 patients who received low dose rh IL-2 after infected CMV or EBV,while 12 continue receiving DMARDs.Treg cells and effector lymphocytes subsets were analyzed by comparing in before and after rh IL-2treatment,and analyses the difference of these cells after rh IL-2 and DMARDS therapy.Result:1.70 patients in Group infection include 16 systemic lupus erythematosus,16 dermatomyositis,14 Sj?gren syndrome,12 Rheumatoid arthritis,6 vasculitis,3mix connective tissue disease and 3 systemic sclerosis.Compared with the Group health,the absolute count of Treg cells in Group treatment-na?ve was significantly low(P<0.05),Th17/Treg was notable increase(p<0.05).Compared with Group treatment-na?ve,T lymphocytes,B lymphocytes,NK cells,the total number of T cells,B cells and NK cells,CD4+T cells and Treg cells are all notable low in Group treatment-DMARDs(P<0.05).And Th17/Treg was significantly increase(P<0.05).2.The T lymphocytes,B lymphocytes,NK cells,the total number of T cells,B cells and NK cells,CD4+T cells,T help cell 1(Th1),T help cell 2(Th2),and Th17 cells are all significantly decrease in Group infection compared with the Group treatment-DMARDs(P<0.05).While the absolute count of Treg cell was no different between the two groups.Th1/Th2 and Th17/Treg are notable decrease(P<0.05).3.After the course of rh IL-2 treatment,there were significant increase in the absolute count of T lymphocytes,B lymphocytes,the total number of T cells,B cells,and NK cells,CD4+ T cells,CD8+ T cells,Th1,Th2,and Treg cells(P<0.01).Th17/Treg was significantly low after treatment.Compared with the patients who continue receiving DMARDs,all lymphocytes subsets in peripheral blood had a rising trend in patients receiving rh IL-2 treatment.Conclusion:The data suggest that the decrease of Treg cell number and imbalance between Th17 and Treg may contribute to the pathogenesis of connective tissue disease.Excessive using glucocorticoid and DMARDs may augment the imbalance of Th17/Treg.On the other hand,these medicines decrease immune function,which leads to EBV and CMV viremia.Over the treatment of rh IL-2,immune function was improved and there was a more significant increase in the absolute count of Treg cells than Th17,and a consequently restore the balance of Th17/Treg.