PD-1 and PDL-1 expression in patients with chronic HIV-1 infection: relationship to CD4%, immune activation and antiretroviral therapy (ART) (46.22)

Abstract

Abstract In chronic HIV-1 infection, CD8 T-cell exhaustion is linked to an increased expression of programmed death molecule (PD-1), a negative regulator of activated T cells. We investigated the relative expression of PD-1 and its ligand PD-L1 in T cells and monocytes of HIV-1 infected patients at different time points of ART. In healthy controls (n=3), <10%of CD4 or CD8 T cells expressed PD-1; in comparison, expression of PD-1 was increased (P<0.05) in treatment naïve patients (n=9) in both CD4 and CD8 T cells. In patients, PD-1 expression on CD4 T cells was correlated with activation marker, HLA-DR (P=0.0004) and inversely related to percentage of CD4 T cells (P=0.0004). Percentage of cells expressing PD-L1 was significantly higher in monocytes (CD14+) versus CD4 T cells and CD8 T cells (P<0.05). Culture of PBMC with cytokines IL-2, IL-7 and IL-15 for 6 days in vitro resulted in increased expression of PD-1 and PD-L1 in CD4 and CD8 T cells, coupled with increased expression of Ki67 and HLA-DR in 3 ART naïve patients. ART was associated with a trend towards decreasing PD-1 expression. We conclude that PD-1 and PDL-1 interaction contributes to CD4 T cell loss in a state of chronic immune activation associated with HIV-1 infection. Supported in part by the “The International Maternal Pediatric Adolescent AIDS Clinical Trials Network of the National Institute of Allergy and Infectious Diseases” (UOI-A141089 and N01-HD-3-3345) and Institutional support.