The Characteristics Of Memory Precursor Effector Cells And Relationship With Memory CD8 T Cell Dysfunction In Chronic HIV-1 Infection

Background:The generation and maintenance of CD8 T memory cells are critical to immune surveillance of the host.It is widely accepted that HIV-1 infected individuals suffer from memory cell depletion,immune dysfunction and immune deficiency,which can lead to opportunistic infections(such as pneumocystis,tuberculosis,etc.).Especially in HIV-1-infected patients with failed immune reconstruction,the mechanism why immune function cannot be restored is still unclear.Long-lived memory cells are differentiated from memory precursor effector cells(MPEC),which are produced during the contraction phase of infection.There has rarely been reported that the characteristics and mechanisms of immune memory T cell depletion of CD8 memory precursor effector cells in chronic HIV-1 infection.Objective:The purpose of this study was to investigate the changes,functional characteristics,and the relationship with disease processes of MPEC in chronic HIV-1infection.Methods:We enrolled 14 healthy controls,89 HIV-1-infected individuals including 50treatment na?ve,26 ART treated complete responders and 13 ART treated immunological non-responders.The phenotypic and functional characteristics of MPEC,levels of plasma cytokines and HIV DNA were detected.The relationship between MPEC and plasma cytokines,viral load,CD4 count as well as HIV DNA were analyzed.Results:(1)Compared with the healthy control group,the frequency and count of MPEC is decreased significantly in peripheral blood of patients with chronic HIV-1 infection.After antiviral treatment,the frequency and count of MPEC showed a significant recovery,but they are still not completely normal.(2)The friquencies of MPEC correlated positively with CD4 count(r=0.40,P=0.0044),positively with CD4/CD8(r=0.50,P=0.0002)and negatively with viral load(r=-0.34,P=0.013)in treatment na?ve patients,suggesting that MPEC may be associated with disease progression.(3)The friquencies of MPEC correlated positively with IL-7,IP-10 in treatment na?ve patients.(4)The reduction of memory cells in chronic HIV-1 infection may be associated with reduced level of serum IL-7 and impaired response to IL-7-mediated p-STAT5 pathway.Conclusions:The decreased frequency and number of CD8~+T MPEC in peripheral blood of patients with chronic HIV-1 infection,may be related to the decreased IL-7 levels as well as the decrease response of MPEC to the IL-7-mediated p-STAT5 pathway that affecting the survival,proliferation,development and immune protection of MPEC.The study clarified the role of MPEC in chronic HIV-1 infection and may provide further understanding for the future therapy of HIV.