The number and function of circulating dendritic cells may limit effector memory CD4+ T-cell responses in HIV patients responding to antiretroviral therapy

Abstract

Some HIV patients who previously experienced severe immunodeficiency retain low pathogen-specific T-cell responses despite a virological response to antiretroviral therapy (ART). To identify correlates with dysfunction in accessory cell populations, HIV patients were stratified into groups maintaining high or low CD4+ T-cell IFN-? responses to cytomegalovirus (CMV) over 4-8 years on ART. Myeloid dendritic cells (mDC), plasmacytoid (p) DC, M-DC8+ cells and monocytes were enumerated and mRNA of cytokines and activation molecules were quantitated in purified subpopulations. Proportions of pDC were lower (p = 0.043) and mDC were higher (p = 0.043) in low responders. TRAIL receptor 2 (DR5) mRNA levels in pDC (p = 0.0008) and mDC (p = 0.0062) were lower in high responders compared to controls. Levels of IL-15 mRNA were higher in mDC from high responders (p = 0.015) and levels of IL-10 mRNA were higher in M-DC8+ cells from low responders (p = 0.036). Hence CMV-specific CD4+ T-cell IFN-? responses may be affected by numbers and function of circulating DC. © 2008 Elsevier Inc. All rights reserved.