Murine cytomegalovirus retinitis during retrovirus-induced immunodeficiency (MAIDS) in mice: interleukin-2 immunotherapy correlates with increased intraocular levels of perforin mRNA.

Published

Journal Article

Mice with a retrovirus-induced immunosuppression (MAIDS) are susceptible to experimental murine cytomegalovirus (MCMV) retinitis, but can be rendered resistant to retinitis by systemic interleukin-2 (IL-2) immunotherapy. Experiments were performed to explore the mechanism by which IL-2 treatment during MAIDS might restore resistance to MCMV retinitis. Whereas 80% of untreated MAIDS mice were susceptible to MCMV retinitis, none (0%) of IL-2-treated MAIDS mice developed necrotizing retinitis. In comparison, 100% of both untreated and IL-2-treated perforin knockout mice (PKO mice) were susceptible to MCMV retinitis, and severity of retinitis and amounts of infectious intraocular MCMV in IL-2-treated PKO mice were equivalent to that in untreated PKO mice. A competitive quantitative RT-PCR assay was used to measure the levels of perforin mRNA within MCMV-infected eyes of immunologically normal mice, untreated MAIDS mice, and IL-2-treated MAIDS mice. Although the level of perforin mRNA within MCMV-infected eyes of untreated MAIDS mice susceptible to retinitis was significantly reduced when compared to the high level found within MCMV-infected eyes of normal mice resistant to retinitis, systemic treatment of MAIDS mice with IL-2 increased perforin mRNA within MCMV-infected eyes to levels found in normal mice. The ability of IL-2 treatment to increase intraocular levels of perforin mRNA diminished with the progression of MAIDS. Our findings support the hypothesis that systemic IL-2 immunotherapy during MAIDS provides protection against MCMV retinitis by upregulation of perforin-mediated cytotoxicity used by cytotoxic lymphocytes to kill virus-infected cells.

Full Text

Duke Authors

Cited Authors

  • Dix, RD; Podack, ER; Cousins, SW

Published Date

  • July 2003

Published In

Volume / Issue

  • 59 / 2

Start / End Page

  • 111 - 119

PubMed ID

  • 12895694

Pubmed Central ID

  • 12895694

International Standard Serial Number (ISSN)

  • 0166-3542

Digital Object Identifier (DOI)

  • 10.1016/s0166-3542(03)00066-4

Language

  • eng

Conference Location

  • Netherlands