Sparing of the ipsilateral retina after anterior chamber inoculation of HSV-1: requirement for either CD4+ or CD8+ T cells.
OBJECTIVE
To determine whether CD4+ T cells, CD8+ T cells, or both CD4+ and CD8+ T cells are required for preservation of the ipsilateral retina after uniocular anterior chamber inoculation of herpes simplex virus type 1 (HSV-1).


METHODS
Adult-thymectomized BALB/c mice were T cell depleted by administration of anti-CD4 monoclonal antibody (mAb), anti-CD8 mAb, or anti-CD4 mAb and anti-CD8 mAb together. Control mice were thymectomized but were not T cell depleted. HSV-1 (KOS) was inoculated in one anterior chamber. At intervals after inoculation, the injected eyes were examined histopathologically or homogenized to determine the kinetics of infectious virus recovery. Additional groups of in vivo depleted mice were injected with wild type KOS and RH116 (a mutant of KOS containing the Escherichia coli beta-galactosidase gene) to determine whether viral genes were expressed in the retina in any of the mice.


RESULTS
In the inoculated eyes of mice depleted of both CD4+ and CD8+ T cells, there was a significantly higher incidence of acute destructive retinitis at days 9 and 14 postinoculation (PI), and the titer of virus recovered at day 14 PI was significantly higher. Viral gene expression in the retina and the optic nerve was observed after day 7 PI only in the group of mice depleted of both CD4+ and CD8+ cells. In contrast, acute destructive retinitis was not observed in nondepleted mice or in mice depleted of either CD4+ or CD8+ T cells alone, and virus recovery was not significantly different among these three groups of mice. No virus-infected cells were observed in the optic nerve or the sensory retina of nondepleted mice, of mice depleted of only CD4+ cells, or of mice depleted of only CD8+ cells.


CONCLUSIONS
The results of these studies suggest that either CD4+ or CD8+ T cells can spare the retina of the injected eye after uniocular anterior chamber inoculation of HSV-1. Because virus appeared after day 7 PI in the ipsilateral optic nerve and retina only in mice depleted of both CD4+ and CD8+ T cells, these results suggest that spread of virus to the ipsilateral retina occurs via the optic nerve and that either CD4+ or CD8+ T cells can prevent spread of virus to the inoculated eye resulting in sparing of the ipsilateral retina.
Azumi
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Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Atherton
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D000818:Animals; D000867:Anterior Chamber / Q000382:microbiology*; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015828:Eye Infections, Viral / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009900:Optic Nerve / Q000382:microbiology / Q000473:pathology; D012160:Retina / Q000382:microbiology / Q000473:pathology; D012173:Retinitis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014779:Virus Replication; D001616:beta-Galactosidase / Q000032:analysis
D000911:Antibodies, Monoclonal; D001616:beta-Galactosidase