IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2007;48:2194-2202.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1321
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Knickelbein, J. E.
Right arrow Articles by Hendricks, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Knickelbein, J. E.
Right arrow Articles by Hendricks, R. L.

Modulation of CD8+ CTL Effector Function by Fibroblasts Derived from the Immunoprivileged Cornea

Jared E. Knickelbein,1,2 Sherrie Divito,1,2 and Robert L. Hendricks2,3,4

1From the Graduate Program in Immunology and the 2Departments of Ophthalmology, 3Molecular Genetics and Biochemistry, and 4Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

PURPOSE. To examine the acquisition of lytic activity and interferon gamma (IFN-{gamma}) production by herpes simplex virus (HSV) type 1-specific CD8+ cytotoxic T-lymphocyte precursors (HSV-CTLps) after exposure to in vitro HSV-1-infected fibroblasts derived from the immunoprivileged cornea (HSV-cFb) or nonprivileged skin (HSV-sFb) or to in vitro HSV-1-infected splenocytes (HSV-Spls) obtained from noninfected mice.

METHODS. Chromium release assays were used to assess HSV-CTL cytotoxicity, and flow cytometry was used to assess intracellular granzyme (Gr) B content and lytic granule exocytosis through surface CD107a expression. In addition, the BLT esterase assay was used to assess functional GrA release. [3H]-Thymidine incorporation and total CD8+ cell numbers, as assessed by flow cytometry, were used to assess CTLp proliferation. ELISA and intracellular flow cytometric analysis were used to assess CTL IFN-{gamma} production and release.

RESULTS. HSV-cFb, HSV-sFb, and HSV-Spl individually induced strong cytotoxic and IFN-{gamma} responses by HSV-CTL. Simultaneous exposure to HSV-Spl and HSV-cFb virtually abrogated the cytotoxic response while enhancing IFN-{gamma} production by HSV-CTL. In contrast, exposure to HSV-sFb, in conjunction with HSV-Spl, did not alter the cytotoxic or IFN-{gamma} response of HSV-CTL compared with stimulation with either cell type alone. Abrogation of the cytotoxic response after simultaneous exposure to HSV-Spl and HSV-cFb was associated with reduced production, storage, or both of GrA and GrB but with unimpaired lytic granule release.

CONCLUSIONS. These findings suggest that an interesting regulatory circuit protects the cornea from the potentially damaging effects of CD8+ T-cell cytotoxic function while maintaining their ability to control virus replication through enhanced production of the antiviral cytokine IFN-{gamma}.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the Association for Research in Vision and Ophthalmology