| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
Departments of
*
Ophthalmology,
Immunology, and
Molecular Genetics and Biochemistry and
Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
Approximately 7 days after HSV-1 corneal infection, BALB/c mice develop tissue-destructive inflammation in the cornea termed herpes stromal keratitis (HSK), as well as periocular skin lesions that are characterized by vesicles, edema, and fur loss. CD4+ T cells and Th1 cytokines contribute to both the immunopathology in the cornea and the eradication of viral replication in the skin. We demonstrate that disruption of CD40/CD154 signaling does not impact the initial expansion of CD4+ T cells in the draining lymph nodes, but dramatically reduces the persistence and Th1 polarization of these cells. Despite the reduced Th1 response, CD154–/– mice developed HSK and periocular skin disease with similar kinetics and severity (as assessed by clinical examination) as wild-type (WT) mice. However, when the composition of the inflammatory infiltrate was examined by flow cytometric analysis, CD154–/– mice exhibited significantly fewer CD4+ and CD8+ T cells and neutrophils than WT mice at the peak of HSK. Moreover, CD4+ T cells from infected corneas of CD154–/– mice produced significantly less IFN-
than those of WT mice when stimulated with viral Ags in vitro. The IFN- production of cells from infected corneas of WT mice was not affected by addition of anti-CD154 mAb to the stimulation cultures. This suggests that CD154 signaling is required at the inductive phase, but not at the effector phase, of the Th1 response within the infected cornea. We conclude that local disruption of CD40/CD154 signaling is not likely to be a useful therapy for HSK.
This article has been cited by other articles:
|
|
 |
|
  D. A. Leib, D. E. Alexander, D. Cox, J. Yin, and T. A. Ferguson Interaction of ICP34.5 with Beclin 1 Modulates Herpes Simplex Virus Type 1 Pathogenesis through Control of CD4+ T-Cell Responses J. Virol., December 1, 2009; 83(23): 12164 - 12171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lepisto, M. Xu, H. Yagita, A. D. Weinberg, and R. L. Hendricks Expression and function of the OX40/OX40L costimulatory pair during herpes stromal keratitis J. Leukoc. Biol., March 1, 2007; 81(3): 766 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Hewitson, G. R. Jenkins, P. A. Hamblin, and A. P. Mountford CD40/CD154 Interactions Are Required for the Optimal Maturation of Skin-Derived APCs and the Induction of Helminth-Specific IFN-{gamma} but Not IL-4. J. Immunol., September 1, 2006; 177(5): 3209 - 3217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, L. C. Hooper, M. S. Chin, C. N. Nagineni, B. Detrick, and J. J. Hooks Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1-human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors. J. Gen. Virol., August 1, 2006; 87(Pt 8): 2161 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lepisto, G. M. Frank, M. Xu, P. M. Stuart, and R. L. Hendricks CD8 T Cells Mediate Transient Herpes Stromal Keratitis in CD4-Deficient Mice. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3400 - 3409. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
