Murine cytomegalovirus retinitis during retrovirus-induced immunodeficiency (MAIDS) in mice: interleukin-2 immunotherapy correlates with increased intraocular levels of perforin mRNA.
Antiviral Res
; 59(2): 111-9, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12895694
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.
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Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Síndrome de Imunodeficiência Adquirida Murina
/
Interleucina-2
/
Retinite por Citomegalovirus
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article