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Protection against Murine Cytomegalovirus Retinitis by Adoptive Transfer of Virus-Specific CD8⁺ T Cells

From the Departments of ¹ Microbiology and ² Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio.

PURPOSE. Human cytomegalovirus retinitis, the most common ophthalmic infection of AIDS patients, has been modeled in BALB/c mice infected with murine cytomegalovirus by the supraciliary route. A series of depletion and adoptive transfer studies was performed to determine whether adoptive transfer of T cells protects mice from retinitis caused by murine cytomegalovirus infection after supraciliary inoculation and to determine which subset of T cells is responsible for protection.

METHODS. BALB/c mice were thymectomized and T cell–depleted by injection of monoclonal antibodies to CD4, CD8, or both. Murine cytomegalovirus (9 x 10² plaque forming units [pfu]) was injected into the supraciliary space. Experimental animals received murine cytomegalovirus-specific T cells or subsets of T cells 2 hours before virus injection, whereas control animals received herpes simplex virus type 1–specific T cells by tail vein injection. Eight days after virus injection, retinal pathology was scored by histopathologic examination of hematoxylin and eosin–stained ocular sections.

RESULTS. CD8⁺ T cell depletion was sufficient for development of retinitis after supraciliary injection of murine cytomegalovirus. Adoptive transfer of murine cytomegalovirus-specific T cells, but not herpes simplex virus type 1–specific T cells, provided protection from retinitis. Additionally, separation of the murine cytomegalovirus-specific T cells into CD8⁺ and CD4⁺ subsets before adoptive transfer showed that the CD8⁺ fraction of the adoptive T cells was responsible for protection.

CONCLUSIONS. These results suggest that adoptive transfer of cytomegalovirus-specific T cells or T cell subsets might be used to treat or prevent cytomegalovirus retinitis in immunosuppressed human patients.

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