ADOPTIVE TRANSFER OF MURINE CYTOMEGALOVIRUS-IMMUNE LYMPH-NODE CELLS PREVENTS RETINITIS IN T-CELL-DEPLETED MICE

Purpose. The purpose of this study was to determine whether adoptive t ransfer of murine cytomegalovirus (MCMV)-immune lymph node cells preve nts retinitis in immunosuppressed mice. Methods. Adult BALB/c mice wer e thymectomized and T-cell depleted using rat monoclonal antibodies sp ecific for mouse CD4(+) and CD8(+) T-cells. The level of rat immunoglo bulin G in the treated mice was monitored by enzyme-linked immunosorbe nt assay. Immune cells were labeled with PKH26-GH immediately before a doptive transfer, and flow cytometry was used to determine the percent age of adoptively transferred T-cells (PKH+, fluorescein isothiocyanat e [FITC+]) in the spleens of the recipient mice 3 days after transfer. The ability of adoptively transferred cells to protect from retinitis tvas studied in T-cell-depleted mice injected with MCMV through the s upraciliary route. Mice received 4 x 10(7) in vitro-restimulated MCMV- immune cells, 4 x 10(7) freshly isolated MCMV-immune cells, 4 x 10(7) freshly isolated ovalbumin-immune cells, or no cells (control group). Results. The best time to balance depletion of endogenous T-cells with persistence of transferred cells was 3 weeks after T-cell depletion. Both restimulated and freshly isolated MCMV-immune cells conferred pro tection from retinitis. Freshly isolated ovalbumin-immune lymph node c ells did not prevent retinitis, indicating that protection was virus-s pecific and merely was not because of transfer of antigen-activated ly mph node cells. Conclusions. Adoptive immunotherapy has been used to p revent cytomegalovirus (CMV) infection in patients who have undergone transplantation, and, by extrapolation, the results of these studies s uggest that adoptive immunotherapy with human CMV-specific immune cell s might be used to prevent or ameliorate CMV retinitis in immunocompro mised patients.