Abstract
Purpose:
Mice with retrovirus-induced immunosuppression (MAIDS) over a 10-week period develop systemic T-cell dysfunction, but without loss of macrophages. We have shown previously that SOCS1 and SOCS3 mRNAs and proteins are highly stimulated during development of experimental retinitis within MCMV-infected eyes of C57BL/6 mice with MAIDS that are susceptible to retinitis (frequency of 80 - 100%). Because others have shown that development of experimental MCMV retinitis in eyes of C57BL/6 mice immunosuppressed by corticosteroid treatment results in significant macrophage loss [Duan et al, 1994] and a reduced frequency of retinitis (~50%) [Zhang et al, 2007], we sought to determine whether SOCS1 and SOCS3 mRNAs are stimulated in MCMV-infected eyes of drug-immunosuppressed mice to the same extent as that observed for SOCS1 and SOCS3 mRNA expression in MCMV-infected eyes of MAIDS mice.
Methods:
Drug-induced immunosuppression was accomplished in healthy C57BL/6 mice by intramuscular injection of methylprednisolone every 3 days beginning at day -2 relative to MCMV inoculation. The left eyes of groups of drug-immunosuppressed C57BL/6 mice were infected with MCMV subretinally; right eyes were mock infected (controls). At 3, 6, and 10 days postinfection, eyes were collected and compared for SOCS1 and SOCS3 mRNA production by quantitative real-time RT-PCR assay.
Results:
Whereas SOCS1 and SOCS3 mRNAs were highly stimulated within MCMV-infected eyes of mice with MAIDS at 6 days postinfection, our present study showed little or no stimulation of SOCS1 and SOCS3 mRNAs within MCMV-infected eyes of drug-immunosuppressed mice at day 6, although there was modest stimulation of these molecules at day 3.
Conclusions:
A comparison of MCMV-infected eyes of drug-immunosuppressed mice and our previous work with MCMV-infected eyes of mice with MAIDS revealed sharply different patterns of SOCS1 and SOCS3 mRNA production during development of retinitis. This surprising outcome may be due to quantitative differences in macrophage populations observed in the two mouse models of experimental MCMV retinitis.