HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sarangi, P. P. Articles by Rouse, B. T. Search for Related Content PubMed PubMed Citation Articles by Sarangi, P. P. Articles by Rouse, B. T.

IL-10 and Natural Regulatory T Cells: Two Independent Anti-Inflammatory Mechanisms in Herpes Simplex Virus-Induced Ocular Immunopathology¹

Pranita P. Sarangi^*, Sharvan Sehrawat^*, Susmit Suvas and Barry T. Rouse^2,*

^* Comparative and Experimental Medicine Program, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996; and Department of Biological Sciences, Oakland University, Rochester, MI 48309

Two prominent anti-inflammatory mechanisms involved in controlling HSV-1-induced corneal immunopathology (stromal keratitis or SK) are the production of the cytokine IL-10 and the activity of natural regulatory T cells (nTregs). It is not known whether, under in vivo conditions, IL-10 and nTregs influence the corneal pathology independently or in concert. In the current study using wild-type and IL-10^–/– animals, we have assessed the activity of nTregs in the absence of IL-10 both under in vitro and in vivo conditions. The IL-10^–/– animals depleted of nTregs before ocular infection showed more severe SK lesions as compared with the undepleted IL-10^–/– animals. In addition, nTregs purified from naive WT and IL-10^–/– animals were equally able to suppress the proliferation and the cytokine production from anti-CD3-stimulated CD4⁺CD25^– T cells in vitro. Furthermore, intracellular cytokine staining results indicated that nonregulatory cells expressing B220 and CD25 markers were the major IL-10-producing cell types in the lymphoid tissues of HSV-infected mice. In contrast, in the infected corneas, cells with the CD11b⁺Gr1⁺ phenotype along with a minor population of Foxp3^–CD4⁺ and a few F4/80⁺ cells produced IL-10. Our current investigations indicate that at least two independent anti-inflammatory mechanisms are involved in limiting the corneal lesions in SK, both of which may need to be modulated to control SK therapeutically.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants EY05093 and AI 1063365.

² Address correspondence and reprint requests to Dr. Barry T. Rouse, M409 Walters Life Sciences Building, Department of Pathobiology, University of Tennessee, 1414 Cumberland Avenue, Knoxville TN 37996-0845. E-mail address: btr{at}utk.edu

³ Abbreviations used in this paper: SK, stromal keratitis; DLN, draining lymph node; p.i., postinfection; nTreg, natural regulatory T cell; TG, trigeminal ganglion; Treg, regulatory T cell; WT, wild type.