Cytokine gene expression and T-cell proliferative responses in lymph node mononuclear cells from children with early stage human immunodeficiency virus infection.

Background and Objectives. The immunologic events taking place in secondary lymphoid tissue from children with early stage human immunodefi- ciency virus (HIV) infection are poorly understood. The aim of this study was to investigate cytokine gene expression and proliferative responses in lymph node (LN) biopsies from five children with ear- ly stage HIV infection, in the context of LN morphol- ogy and viral load. Design and Methods. The design of the study was approved by the local Ethical Committee. Cytokine gene expression was studied in LN biopsies and in paired peripheral blood (PB) samples from HIV- infected children by reverse transcriptase-poly- merase chain reaction. T-cell proliferation was assessed by 3H-thymidine incorporation. Viral bur- den in germinal centers was assessed by video den- sitometric analysis following immunohistochemical staining for HIV p24. Results. Interleukin (IL)-2, IL-4 and IL-5 mRNA were not detected in any LN or PB sample from HIV-infect- ed children. Interferon (IFN)-γ mRNA was found only in CD8+ cells. IL-12 p35, IL-10, transforming growth factor-(TGF)-β1, regulated on activation normal T- cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, MIP-1β and IL-16 transcripts were detected in all samples. Prolifera- tion of LN and PB mononuclear cells to polyclonal mitogens and soluble (recall and HIV-related) anti- gens was impaired as compared with the responses in a group of age-matched healthy controls. Interpretation and Conclusions. Changes in cytokine gene expression and T-cell proliferative responses are already detectable in lymph nodes from HIV- infected children at an early stage of disease.