ABSTRACT
Objective To compare the synchronous changes of high risk human papillomavirus load(HPV-DNA)and CD4+CD25+Foxp3+regulatory T cells(Treg)in local microenvironment of cervix,and investigate the ef-fects of HPV virus replication and progression of cervical lesions on Treg cells. Methods 304 cases of HR-HPV infection with cervical lesions were divided into 5 groups,cervical intraepithelial neoplasia(CIN)I,CINII,CINIII, cervical cancer and chronic cervicitis.The HPV-DNA of cervical secretion was detected by PCR fluorescence,and the relative Treg cells numbers from cervical brush samples were determined by flow cytometry with CD4+CD25+Foxp3+gating,and the data were statistically analyzed. Results(1)There was significant difference of cervical Treg cells in different degrees of cervical lesion and different copy numbers by variance comparison(F = 24.93, 109.86,P < 0.05),and a further pairwise comparison showed that there was no significant difference of Treg cell between chronic cervicitis and CINI and low load(HPV DNA 104~105copies/mL)and medium load(HPV DNA 105~106copies/mL)(P>0.05).There was a significant difference between the other groups(P<0.05);(2)Treg cells as variable,interaction effect of cervical lesions and viral load factors were significant different(F=3.39,P<0.05). The effect of different cervical lesions and HR-HPV viral load on the expression of Treg cells was differen-tial. An overall showing with the degree of cervical lesions increased,HR-HPV virus copy number increased, Treg cells expression increased gradually;(3)CD4+CD25+Foxp3+Treg cells were highly expressed in cervical cancer patients,but the expression level fluctuated widely and the numerical distribution was the most dispersedly. Conclusion The immune suppression function of local CD4+CD25+Foxp3+Treg cells with different cervical lesions and different HR-HPV DNA may bilaterally regulate the prognosis of cervical lesions,as a whole,between Treg cells and HR-HPV load and cervical lesions were the consistent progress trend.
ABSTRACT
Regulatory T (Treg) cells is an indispensable subset of T lymphocyte with the ability of immunosuppression in the periphery.Thymus-derived Treg cells(CD4+CD25+FOXP3+Treg cells) play a fundamental role in maintaining immune homeostasis in vivo.Treg cells have been actively involved in the onset and development of major human diseases including malignant tumors, autoimmune diseases,infectious diseases,allergic diseases and graft versus host disease(GVHD).Exosomes are membranous vesicles of endosomal origin that released from multiple cells into the extracellular space.They are currently considered to be vehicles containing protein,RNA and MicroRNA which can been transferred to recipient cells to modulate their activity by cell-contact-independent mecha-nism.Exosomes have a great impact on the induction and proliferation of Treg cells,understanding the relation of them will lead to novel therapeutic approaches for cancer immunotherapy,treating autoimmunity,infection,allergy and organ transplantation.
ABSTRACT
Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)％ vs (2.40±1.11)％,t=13.89,P=0.000; (8.33±2.03)％ vs (1.99± 0.86)％,t=12.93,P=0.000; (5.65±1.55)％ vs (1.32±0.73)％,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.