HIV TYPE-1 INDUCTION OF INTERLEUKIN-1 AND INTERLEUKIN-6 PRODUCTION BYHUMAN THYMIC CELLS

In vitro and in vivo studies have demonstrated that HIV can infect thy mocytes at different maturational stages and lead to changes in the th ymic microenvironment. To determine the effect of HIV on thymic stroma l cells and the production of cytokines important in thymocyte develop ment, three types of adherent thymic cultures were established and stu died: thymic epithelial cells (TECs), macrophage-enriched, and mixed c ultures of macrophages and TECs (M phi/TEC). Cultures were exposed to HIV-1 strains HIV-1(IIIB) and HIV-1(Ba-L), and studied from day 2 to d ay 26 for the presence of infection, cytopathology, and cytokine (IL-1 alpha, IL-1 beta, and IL-6) production. M phi/TEC and macrophage-enri ched cultures were infected by both HIV strains without cytopathic cha nges. The TECs grew well in culture for at least 6 weeks and showed no evidence of infection, cytopathology, or changes in cytokine producti on with HIV. Only cultures containing macrophages (M phi/TEC or macrop hage enriched) showed changes in cytokine production with HIV. Sustain ed production of IL-1 alpha was seen for up to 20 days, with small or no increases in IL-1 beta. M phi/TEC and TEC cultures produced high co nstitutive levels of IL-6 that were not changed by HIV. Unstimulated m acrophage-enriched cultures produced small amounts of IL-6 that were i ncreased by HIV 20-fold. This study suggests that HIV infection in viv o can lead to infection of thymic macrophages resulting in cytokine ab normalities and a constant source for HIV to infect maturing thymocyte s. These cytokine effects could lead to abnormal maturation and contri bute to the lack of regeneration of the mature CD4(+) T cell pool.