Kinetics of cytokine production by thymocytes during murine AIDS caused by LP-BM5 retrovirus infection

C57BL/6 mice inoculated with the murine leukemia retrovirus mixture, LP-BM5, rapidly produce murine AIDS with many functional similarities to human AIDS. Human HIV infection has recently been shown to inhibit thymocyte maturation. Therefore, the kinetics of the proliferation of thymocytes induced by Concanavalin A (ConA) and levels of cytokines produced by in vitro ConA-stimulated thymocytes were examined during the progression of murine AIDS. The proliferation of thymocytes induced by ConA was significantly enhanced by retrovirus infection at 4 weeks post-infection compared to control, but significantly inhibited during 8-12 weeks post-infection. Release of IL-2 by ConA-stimulated thymocytes was significantly increased by retrovirus infection during 2-5 weeks post-infection and 11-18 weeks post-infection compared to control, but significantly decreased during 7-9 weeks post-infection. Secretion of IL-4 by ConA-stimulated thymocytes was significantly enhanced by retrovirus infection from 5 to 18 weeks post-infection compared to control. The level of IL-6 produced by ConA-stimulated thymocytes was significantly inhibited by retrovirus infection at the beginning of retrovirus infection (2-9 weeks), but significantly elevated after 11 weeks post-infection compared to control. Release of IFN_γ by ConA-stimulated thymocytes, however, was significantly enhanced during the whole period of retrovirus infection compared to control, while it surged at 13 weeks post-infection. We conclude that retrovirus infection affects the thymus, producing altered T-cell differentiation via the dysregulation of thymocyte cytokine secretion.