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C.O. Ekworomadu, S.W. Cousins, R.D. Dix; Adoptive Transfer of Immune Cells from MCMV-Immunized gld Mice Protect against MCMV Retinitis in Nonimmunized PKO Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4620.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have shown previously that mice deficient in the perforin cytotoxic pathway (PKO mice) are susceptible to MCMV retinitis. Conversely, mice deficient in the Fas/FasL cytotoxic pathway (gld mice) exhibit a resistance to MCMV retinitis that is observed in immunologically normal mice. To confirm the importance of the Fas/FasL pathway in protection against MCMV retinitis, adoptive transfer studies were performed to test the hypothesis that PKO mice can be rendered resistant to retinitis by transfer of immune cells from MCMV-immunized gld mice. Methods: Groups of PKO mice were injected intravenously with 2 to 5 million freshly-isolated splenic cells from MCMV-immunized normal C57BL/6 mice, gld mice, or PKO mice. Controls include C57BL/6 mice immunosuppressed with methylprednisolone (2mg, day –2, +2, and +6) that received freshly-isolated splenic cells from MCMV-immunized or nonimmunized normal C57BL/6 mice. All mice were then challenged with MCMV by subretinal injection. MCMV-inoculated eyes from all mice were collected 8-10 days following subretinal MCMV injection, analyzed histopathologically, and scored for frequency and severity of necrotizing retinitis. Results: As expected, adoptive transfer of immune cells reduced the frequency of MCMV retinitis in corticosteroid-immunosuppressed C57BL/6 mice (3/8) when compared with control animals (7/7). Similarly, adoptive transfer of immune cells from either MCMV-immunized normal C57BL/6 or gld mice reduced the frequency of MCMV retinitis in nonimmunized PKO mice (2/5 and 2/6, respectively). In sharp contrast, no protection was observed in nonimmunized PKO mice that received immune cells from MCMV-immunized PKO mice (3/3). Conclusions: Whereas adoptive transfer of immune cells from normal C57BL/6 mice and gld mice provided protection against MCMV retinitis in nonimmunized PKO mice, frequency and severity of retinitis was unaffected in nonimmunized PKO mice when receiving adoptively transferred immune cells from PKO mice. These results underscore the importance of the Fas/FasL pathway in protection against MCMV retinitis.
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