Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection

Abstract

Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic cells (DCs) are required for specific antigen presentation to naive T lymphocytes and for antiviral, type I interferon secretion. Two major blood DC populations are found: CD11c⁺ (myeloid) DCs, which secrete IL-12, and CD123⁺ (IL-3–receptor⁺) DCs (lymphoid), which secrete type I interferons in response to viral stimuli. The authors have previously found a decreased proportion of blood CD11c⁺ DCs in chronic HIV⁺ patients. In this study, 26 to 57 days after infection and before treatment, CD123⁺ and CD11c⁺ DC numbers were dramatically reduced in 13 HIV⁺ patients compared with 13 controls (P = .0002 and P = .001, respectively). After 6 to 12 months of highly active antiretroviral therapy, DC subpopulation average numbers remained low, but CD123⁺ DC numbers increased again in 5 of 13 patients. A strong correlation was found between this increase and CD4 T-cell count increase (P = .0009) and plasma viral load decrease (P = .009). Reduced DC numbers may participate in the functional impairment of HIV-specific CD4⁺ T cells and be responsible for the low type I interferon responsiveness already known in HIV infection. The restoration of DC numbers may be predictive of immune restoration and may be a goal for immunotherapy to enhance viral control in a larger proportion of patients.