RANTES Production in HIV‐1 Antigen‐Stimulated Whole Blood Culture: Relationship with Type 1 Immune Response and Plasma Viral Load in Individuals Infected with HIV‐1

Abstract
Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other β‐chemokines may be HIV‐1‐suppressive factors but their role in the progression of HIV‐1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV‐1. We used whole blood culture to study the production of RANTES, interferon (IFN)‐γ, interleukin (IL)‐4 and IL‐13 in response to supernatant of T cells infected with HIV‐1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL‐4 and/or IL‐13 > IFN‐γ). We obtained a positive correlation between RANTES and IFN‐γ (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN‐γ/IL‐4 (P = 0.04) and IFN‐γ/IL‐13 (P = 0.003), and a negative correlation between RANTES production and HIV‐1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV‐1 p24‐stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV‐1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV‐1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV‐1 replication.