Homeostasis of chemokines, interferon production and lymphocyte subsets: implications for AIDS pathogenesis

Certain individuals with elevated levels of macrophage inflammatory protein (MIP)1 alpha, MIP1 beta and RANTES expression appear to be resistant to human immunodeficiency virus (HIV) infection. In this work, we demonstrate that chemokines production by peripheral blood mononuclear cells (PBMCs) are homeostatic parameters varying from one individual to another, and we define optimized experimental conditions to reproducibly assess these parameters. We also studied alpha- and gamma-interferons (IFN alpha and IFN gamma, respectively) which have been implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS). The kinetics of production of all these cytokines by fresh PBMCs were determined upon stimulation with phytohemagglutinin (PHA), staphylococcus enterotoxin b (SEB) and purified protein derivative (PPD). RANTES and MIP1 alpha are produced early in response to activation, followed by MIP1 beta, (alpha-interferon, gamma-interferon, alpha IFN, gamma-IFN alpha and IFN alpha and gamma. These results suggest that using our methodology, chemokines levels can be reliably determined, permitting the performance of accurate genetic studies using PBMCs from various cohorts (siblings or AIDS related cohorts).