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

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.

• Authors: Richard D Dix, Eckhard R Podack, Scott W Cousins
• Journal: Antiviral research (Antiviral Res) Vol. 59 Issue 2 Pg. 111-9 (Jul 2003) ISSN: 0166-3542 [Print] Netherlands
• PMID: 12895694 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-2
• Membrane Glycoproteins
• Pore Forming Cytotoxic Proteins
• RNA, Messenger
• Recombinant Proteins
• Perforin

Topics

• Animals
• Base Sequence
• Cytomegalovirus Retinitis (etiology, immunology, prevention & control)
• Cytotoxicity, Immunologic
• Eye (immunology, metabolism)
• Immunotherapy
• Interleukin-2 (therapeutic use)
• Membrane Glycoproteins (deficiency, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Murine Acquired Immunodeficiency Syndrome (complications, immunology, therapy)
• Perforin
• Pore Forming Cytotoxic Proteins
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (therapeutic use)