NK cell modulation of murine cytomegalovirus retinitis

CMV retinitis, the most common ophthalmic infection of AIDS patients, causes blindness if left untreated. To study the role of NK cells in the modulation of CMV ocular infection, 9.0 x 10(2) plaque-forming units of the Smith strain of murine CMV (MCMV) was injected into the supraciliary space of the left eyes of BALB/c mice. Lysis of NK-sensitive target cells (YAC-1) by effectors from the draining lymph nodes peaked at day 5 postinfection, while the splenic cytolytic response was biphasic, with peaks at days 2 and 7 postinfection. Flow cytometry showed that NK cells (DX-5+) increased in spleens and eyes 5 days after supraciliary infection with MCMV compared with uninfected or mock-infected controls. Eight days after supraciliary injection with 9.0 x 10(2) plaque-forming units of MCMV, 7 of 10 NK-depleted mice developed retinitis compared with only 2 of 10 non-NK-depleted control mice. Poly(I-C) activation of NK cells in T cell-depleted animals protected mice from MCMV retinitis; only 2 of 10 mice in the poly(I-C)-treated group developed retinitis compared with 8 of 10 T cell-depleted, non-poly(I-C)-treated control mice. These results show the importance of NK cells in preventing MCMV retinitis and suggest that NK cells may also be involved in modulation of cytomegalovirus retinitis in human patients.