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Published online before print October 20, 2004

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(Journal of Leukocyte Biology. 2005;77:24-32.)
© 2005 by Society for Leukocyte Biology

Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis

Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville

¹ Correspondence: M409 Walters Life Sciences Bldg., University of Tennessee, Knoxville, TN 37996-0845. E-mail: btr{at}utk.edu

Herpetic stromal keratitis (HSK) results in postinfection with Herpes simplex virus type 1 (HSV-1). The pathogenesis involves tissue damage by the host immune system, classifying HSK as an immunopathological disease. The crucial disease orchestrating cells is thought to be the T lymphocytes. The present study elucidates pathogenic and protective T cell subsets involved in the development of HSK using the gBT mice, which possess a monoclonal population of CD8⁺ T cells reactive to a HSV immunodominant epitope. Results show that HSV-reactive CD8⁺ T cells enter infected corneas during the acute but not the chronic phase of the disease during which the predominant population is CD4⁺ T cells. Adoptive transfer experiments in T and B cell-deficient recombination-activating gene knockout mice revealed that HSV-reactive CD8⁺ T cells are capable of ocular virus clearance, possibly through a combination of corneal and peripheral nervous system antiviral effects, but are not involved in lesion development. CD4⁺ T cells of the virus-specific or nonspecific species emerged as the pathogenic T cells capable of precipitating disease. These observations have the potential to yield important treatment strategies by targeting specific cell types in HSK.

Key Words: immunopathology • Herpes virus • cornea • T lymphocyte

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