LOCALIZATION OF QUINOLINIC ACID IN THE MURINE AIDS MODEL OF RETROVIRUS-INDUCED IMMUNODEFICIENCY - IMPLICATIONS FOR NEUROTOXICITY AND DENDRITIC CELL IMMUNOPATHOGENESIS

Objective and design: Using murine AIDS (MAIDS) as a model of retrovir us-induced immunodeficiency, the aims of this study were (1) to determ ine the cellular source(s) of quinolinic acid (Quin) with regard to it s significance as a potential neuroexcitotoxin in AIDS dementia comple x, and (2) to characterize the relationship between dendritic cell Qui n immunoreactivity and the histopathological changes associated with t he progression of disease. Methods: Mice with MAIDS were sacrificed fr om 1 to 16 weeks post-infection. Temporal and spatial changes in the i n vivo distribution of Quin at the cellular level were determined by c arbodiimide-based immunohistochemical methods. Results: Cellular Quin immunoreactivity was chronically elevated in lymphoid tissues of mice with MAIDS. In contrast, no cellular Quin immunoreactivity was visible in the brain parenchyma at any timepoint studied. Conclusion: These f indings are consistent with the view that select immune cells in the p eripheral lymphoid tissues may be the primary source of Quin, which ma y contribute to neurotoxic complications in retrovirus-induced immunod eficiency syndromes. The predominant Quin immunoreactive cell types ch anged with the progression of disease. A significant finding was the m arked increase in the number of Quin immunoreactive dendritic cells in the early phase of MAIDS, suggesting a relationship between dendritic cells and Quin in retroviral infection.