Protection against murine cytomegalovirus retinitis by adoptive transfer of virus-specific CD8+ T cells.
OBJECTIVE
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 10(2) 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.
Bigger
J E
JE
Department of Microbiology, The University of Texas Health Science Center at San Antonio, 78229,USA.
Tanigawa
M
M
Thomas
C A
CA
Atherton
S S
SS
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015828:Eye Infections, Viral / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000166:cytology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000502:physiology*; D012173:Retinitis / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D013934:Thymectomy