Immune effector cell (IEC)-mediated protection from HSV-1 retinitis occurs in the brain.
Following uniocular anterior chamber inoculation of the KOS strain of HSV-1 into euthymic BALB/c mice, virus spreads from the injected eye to the brain and from the brain to the optic nerve and retina of the uninjected eye resulting in retinitis. Adoptive transfer of HSV-1-specific immune effector cells (IEC) within 24 h of anterior chamber inoculation of virus prevents retinitis. To determine where protection occurs, mice were injected with HSV-1 via the anterior chamber route, and fluorescently-labeled HSV-1-specific-IEC or ovalbumin-specific-lymph node cells were adoptively transferred intravenously. The eyes and brains of these mice were sectioned and examined for virus-infected cells and for fluorescently-labeled adoptively transferred cells. None of the mice in the group receiving an adoptive transfer of virus-specific IEC had evidence of virus infection of the ipsilateral suprachiasmatic nucleus (SCN), whereas the ipsilateral SCN of all of the mice in the control groups were virus-positive by day 5 P.I. Since virus spreads from the ipsilateral SCN to the contralateral optic nerve and retina to cause retinitis in the uninoculated eye, the results of these studies suggest IEC-mediated protection from HSV-1 retinitis occurs proximal to the ipsilateral SCN. Furthermore, since only HSV-1-specific IEC conferred protection and only these cells were observed in the brain, protection and trafficking of cells after adoptive transfer was virus-specific.
Zhao
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M
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284, USA.
Atherton
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SS
D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D012173:Retinitis / Q000517:prevention & control* / Q000821:virology*; D013493:Suprachiasmatic Nucleus / Q000821:virology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*