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EE Kozlowska, SW Cousins, CO Ekworomadu, RD Dix; MCMV Retinitis During MAIDS Correlates With Elevated Levels Of Interleukin-4 mRNA Within MCMV-infected Eyes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2244.
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Purpose: We have shown previously that mice deficient in the perforin pathway of cytotoxicity are susceptible to retinitis following subretinal MCMV inoculation. Moreover, MCMV-infected eyes of mice with retrovirus-induced immunodeficiency (MAIDS) who are destined to develop retinitis also exhibit a significant decrease in levels of perforin mRNA. Since interleukin-4 (IL-4) has been reported to inhibit CD4+ Th1 cells and inhibit virus clearance by limiting the long-term functional capacity of cytotoxic CD8+ T cells, we hypothesized that susceptibility to MCMV retinitis during MAIDS correlates with elevated levels of IL-4 mRNA within MCMV-infected eyes. Methods: Groups of normal C57BL/6 mice or C57BL/6 mice with MAIDS of 8-weeks duration were inoculated with MCMV by uniocular subretinal injection. MCMV-infected eyes and uninfected contralateral eyes were collected from all mice 5 days later, individually homogenized, and individually analyzed for amounts of IL-4 mRNA by RT-PCR and real time PCR assays. Results: IL-4 mRNA was detected in individual MCMV-infected eyes of mice with MAIDS at levels 10 times greater than that detected in individual eyes of contralateral uninfected eyes. Conclusion: MCMV-infected eyes of mice with MAIDS who are destined to develop retinitis showed a 10-fold increase in IL-4 mRNA levels when compared with uninfected contralateral eyes. This result is in agreement with our previous finding that MCMV retinitis during MAIDS correlates with elevated levels of IL-4 within MCMV-infected eyes as measured by ELISA. These findings might explain our ability to restore resistance to retinitis during MAIDS by immunotherapy with interleukin-2 (IL-2), since IL-4 has been reported to impair the ability of differentiated cytotoxic CD8+ T cells to synthesize IL-2 and proliferate. We conclude that MCMV retinitis during MAIDS correlates with elevated levels of IL-4 mRNA within MCMV-infected eyes at a time with perforin mRNA levels are decreased significantly.
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