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Published online before print December 21, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0406293

Received for publication April 26, 2006.
Revised October 20, 2006.
Accepted for publication October 22, 2006.

Article

Expression and function of the OX40/OX40L costimulatory pair during herpes stromal keratitis

Andrew J. Lepisto ^*, Min Xu , Hideo Yagita , Andrew D. Weinberg ^||, and Robert L. Hendricks ^*¶#@

Departments of *Ophthalmology, ^¶Immunology, and ^#Molecular Genetics and Biochemistry and Graduate Program in Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and ^||Earl A. Chiles Research Institute, Providence Medical Center, Portland, Oregon, USA

^@ To whom correspondence should be addressed. E-mail: hendricksrr{at}msx.upmc.edu.

	Abstract

Herpes stromal keratitis (HSK) is an immunopathological disease regulated by Th1 CD4 T cells, which require APC and costimulation within the infected cornea to mediate disease. Recent studies suggest the OX40:OX40 ligand (OX40L) interaction enhances effector cell cytokine secretion at inflammatory sites. OX40⁺ cells were detected in HSV-1-infected mouse corneas as early as 3 days postinfection (dpi), prior to the onset of HSK, and their frequency increased through 15 dpi, when all mice exhibited severe HSK. OX40L⁺ cells were first detected at 7 dpi, coincident with the initiation of HSK. It is interesting that the OX40L⁺ cells did not coexpress MHC Class II or the dendritic cell (DC) marker CD11c. Our findings demonstrate rapid infiltration of activated (OX40⁺) CD4⁺ T cells into HSV-1-infected corneas and expression of OX40L on MHC Class II-negative cells but surprisingly, not on MHC Class II⁺ CD11C⁺ DC, which are present in the infected corneas and required for HSK. Moreover, neither local nor systemic treatment of mice with a blocking antibody to OX40L or with a blocking fusion protein altered the course of HSK significantly, possibly as a result of a lack of OX40L expression on functional APC.

Key Words: HSV-1 • CD4 • mouse • cornea • immunopathology