Interleukin-2 Immunotherapy of Murine Cytomegalovirus Retinitis during MAIDS Correlates with Increased Intraocular CD8+ T-Cell Infiltration

Abstract

AIDS-related human cytomegalovirus retinitis continues to be an important sight-threatening disease in AIDS patients who do not respond to highly active antiretroviral therapy. We have shown previously that systemic cytokine immunotherapy with interleukin-2 (IL-2) will protect against experimental murine cytomegalovirus (MCMV) in mice with a murine retrovirus-induced immunodeficiency syndrome (MAIDS). Since IL-2 serves as a Th1 immunoregulatory cytokine, we hypothesized that IL-2-induced protection against MCMV retinitis during MAIDS would correlate with a measurable increase in the number of natural killer (NK) cells and/or CD8+ T cells that infiltrate the eye in response to MCMV infection of the retina. We therefore performed a study to quantify and compare the number of NK cells and CD8+ T cells that infiltrate MCMV-infected eyes in untreated and IL-2-treated mice with MAIDS at 3 days and 5 days after subretinal MCMV inoculation. Double-label flow cytometric analysis revealed the detection of measurable numbers of both NK cells and CD8+ T cells in MCMV-infected eyes of untreated MAIDS mice destined to develop retinitis. In contrast, IL-2 immunotherapy during MAIDS correlated with a 10-fold increase by day 5 after inoculation in the number of CD8+ T cells in MCMV-infected eyes destined to be resistant to retinitis. However, IL-2 immunotherapy during MAIDS had no appreciable effect on the number of NK cells that infiltrated MCMV-infected eyes. Taken together, our findings suggest that function of cytotoxic lymphocytes that infiltrate the eye may be more important than absolute numbers of cytotoxic lymphocytes that infiltrate the eye when assessing the protective effects of IL-2 immunotherapy on MCMV retinitis during MAIDS.