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

Richard D. Dix, Eckhard R. Podack, Scott W. Cousins

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalAntiviral Research
Volume59
Issue number2
DOIs
StatePublished - Jul 1 2003

Keywords

  • AIDS
  • Cytokine immunotherapy
  • Cytomegalovirus retinitis
  • Interleukin-2
  • MAIDS
  • Perforin cytotoxicity

ASJC Scopus subject areas

  • Virology
  • Pharmacology

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