Role Of Plasma Exosomes On Function Of T Cell And Its Relationship With CD4/CD8 In HIV-1 Infected Patients

Background:After receiving long-term of effective cART(combined Anti-retroviral Treatment),the CD4+T cell count of complete responders(CRs)can be restored up to 350 cells/uL.While in some patients,the CD4/CD8 ratios can not returned to normal,and CD8+T cells show high level of activation and senescence.The purpose of this study was to investigate the characteristics of plasma exosomes in HIV-1 infected patients that,the potential role of plasma exosomes on T cells,and the correlation between plasma exosomes and CD4/CD8 ratio.Methods:Twenty-one complete responders(CRs)with chronic HIV-1 infection were enrolled in this study.According to the CD4/CD8 ratio,the patients were divided into abnormal group(CD4/CD8>0.8)and normalized group(CD4/CD8>0.8)based on their HIV viral load and CD4+T cell count(All of the CRs have received cART for more than 2 years,the HIV viral load was under 20 copies for more than 2 years,and the CD4 T>350 count/ul).Five healthy control(HC)were enrolled.(1)We compared the concentrations of plasma exosomes in different groups and analyzed the correlation between exosomes and CD4/CD8 ratio.(2)The serum-derived exosomes from different patients were co-cultured with fresh PBMC from a healthy person.The effects of exosomes on the function of CD8+T cells were observed.(3)The impacts of exosomes on the function of CD4+T cells were investigated.(4)The effects of exosomes from different groups on the proliferation of CD8+T cells were detected.Findings:(1)The concentration of exosomes in abnormal non-normal group(CD4/CD8<0.8)was significantly higher than that in normalized group(CD4/CD8>0.8)and the HC group.The concentration of plasma exosomes was negatively correlated with the CD4/CD8 ratio of CR patients(r=-0.661,P=0.044).(2)plasma exosomes in abnormal group have capacity to reduce the frequency of CD38 and HLA-DR co-expression on CD8+ Tcells,and the frequency was positively correlated with the CD4/CD8 ratio of patients(r= 0.478,P= 0.039).(3)plasma exosomes from abnormal group inhibited IFN-Y and IL-2 secretion in CD8+T cells,and the inhibitory effect was correlated with CD4/CD8 ratio(r=0.603,P= 0.004;r= 0.700,P<0.001).(4)plasma exosomes from abnormal group were able to inhibit the proliferation of CD8+T cells,and there was a significant positive correlation between the inhibitory effect and the patients' CD4/CD8 ratio.(r= 0.716,P<0.001).(5)plasma exosomes from abnormal group inhibited the activation and the IL-2 level of CD4+T cells,the inhibitory effects were positively correlated with CD4/CD8 ratio(r=0.507,P= 0.027;r= 0.778,P<0.001).Interpretation:The concentration of exosomes in patients with abnormal CD4/CD8 ratio was significantly higher than that in normalized group and healthy controls.Along with the CD4/CD8 recovery,the concentration of exosomes in plasma was significantly reduced to normal.The production of IFN-? and IL-2 in CD8+T cells,the activation of CD4+T cells and CD8+T cells,the proliferation of CD8+T cells were significantly suppressed by plasma exosomes from abnormal group.Our results indicated that elevated exosomes in HIV patients with abnormal CD4/CD8 ratio had an inhibitory effect on over-activation and function of T cells.