1887

Abstract

BALB/c mice infected with the Moscow strain of (ECTV-MOS) show a large number of apoptotic cells, and an influx of lymphoid cells in the epithelium and substantia propria of conjunctivae, respectively. The presence of ECTV-MOS antigens in the epithelium of conjunctivae significantly upregulates Fas in the epithelial layer and FasL in the suprabasal layer of conjunctiva. Inhibition of FasL with blocking antibodies in cultures of conjunctival cells isolated from ECTV-MOS-infected BALB/c mice showed that the Fas/FasL pathway is important in apoptosis of ECTV-MOS-infected cells. The results also showed that the presence of cytokines, in particular interferon (IFN)-, upregulated expression of Fas. Interleukin (IL) 2, 4, 10 and IFN- were produced at the peak of conjunctivitis (at day 15 of infection) with a predominance of IFN- and a small, but significant, production of IL4 and IL10 compared with non-infected animals. These results suggest that not only is Fas/FasL expression in conjunctiva involved in elimination of migrating Fas cells but also plays an important role in the turnover of conjunctival epithelium and thus may be crucial for ECTV spreading to the surrounding environment.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80709-0
2005-07-01
2019-10-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/7/vir862007.html?itemId=/content/journal/jgv/10.1099/vir.0.80709-0&mimeType=html&fmt=ahah

References

  1. Ashkenazi, A. & Dixit, V. M. ( 1998; ). Death receptors: signaling and modulation. Science 281, 1305–1308.[CrossRef]
    [Google Scholar]
  2. Bourcier, T., De Saint-Jean, M., Brignole, F., Goguel, A. & Baudouin, C. ( 2000; ). Expression of CD40 and CD40 ligand in the human conjunctival epithelium. Invest Ophthalmol Vis Sci 41, 120–126.
    [Google Scholar]
  3. Brick, D. J., Burke, R. D., Minkley, A. A. & Upton, C. ( 2000; ). Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to UV light-induced apoptosis. J Gen Virol 81, 1087–1097.
    [Google Scholar]
  4. Brignole, F., De Saint-Jean, M., Goldschild, M., Becquet, F., Goguel, A. & Baudouin, C. ( 1998; ). Expression of Fas-Fas ligand antigens and apoptotic marker APO2.7 by the human conjunctival epithelium. Positive correlation with class II HLA DR expression in inflammatory ocular surface disorders. Exp Eye Res 67, 687–697.[CrossRef]
    [Google Scholar]
  5. Brignole, F., Pisella, P. J., De Saint Jean, M., Goldschild, M., Goguel, A. & Baudouin, C. ( 2001; ). Flow cytometric analysis of inflammatory markers in KCS: 6-month treatment with topical cyclosporin A. Invest Ophthalmol Vis Sci 42, 90–95.
    [Google Scholar]
  6. Buller, R. M. & Palumbo, G. J. ( 1991; ). Poxvirus pathogenesis. Microbiol Rev 55, 80–122.
    [Google Scholar]
  7. Cespedes, I. S., Toka, F. N., Schollenberger, A., Gierynska, M. & Niemialtowski, M. ( 2001; ). Pathogenesis of mousepox in H-2d mice: evidence for MHC class I-restricted CD8+ and MHC class II-restricted CD4+ CTL antiviral activity in the lymph nodes, spleen and skin, but not in the conjunctivae. Microbes Infect 3, 1063–1072.[CrossRef]
    [Google Scholar]
  8. De Saint Jean, M., Brignole, F., Feldmann, G., Goguel, A. & Baudouin, C. ( 1999; ). Interferon-γ induces apoptosis and expression of inflammation-related proteins in Chang conjunctival cells. Invest Ophthalmol Vis Sci 40, 2199–2212.
    [Google Scholar]
  9. De Saint Jean, M., Debbasch, C., Rahmani, M., Brignole, F., Feldmann, G., Warnet, J. M. & Baudouin, C. ( 2000; ). Fas- and interferon γ-induced apoptosis in Chang conjunctival cells: further investigations. Invest Ophthalmol Vis Sci 41, 2531–2543.
    [Google Scholar]
  10. Doymaz, M. Z. & Rouse, B. T. ( 1992; ). Herpetic stromal keratitis: an immunopathologic disease mediated by CD4+ T lymphocytes. Invest Ophthalmol Vis Sci 33, 2165–2173.
    [Google Scholar]
  11. Fenner, F. R. & Buller, M. L. ( 1997; ). Mousepox. In Viral Pathogenesis, pp. 535–553. Edited by N. Nathanson. Philadelphia: Lippincott Raven.
  12. Ferguson, T. A., Green, D. R. & Griffith, T. S. ( 2002; ). Cell death and immune privilege. Int Rev Immunol 21, 153–172.[CrossRef]
    [Google Scholar]
  13. Gao, J., Schwalb, T. A., Addeo, J. V., Ghosn, C. R. & Stern, M. E. ( 1998; ). The role of apoptosis in the pathogenesis of canine keratoconjunctivitis sicca: the effect of topical Cyclosporin A therapy. Cornea 17, 654–663.[CrossRef]
    [Google Scholar]
  14. Gery, I. & Streilein, J. W. ( 1994; ). Autoimmunity in the eye and its regulation. Curr Opin Immunol 6, 938–945.[CrossRef]
    [Google Scholar]
  15. Gierynska, M., Toka, F. N., Cespedes, I. S., Schollenberger, A., Malicka, E., Popis, A. & Niemialtowski, M. G. ( 2000; ). Homing studies on distribution of ectromelia (mousepox) virus-specific T cells adoptively transferred into syngeneic H-2d mice: paradigm of lymphocyte migration. Viral Immunol 13, 107–123.[CrossRef]
    [Google Scholar]
  16. Granville, D. J., Carthy, C. M., Yang, D., Hunt, D. W. & McManus, B. M. ( 1998; ). Interaction of viral proteins with host cell death machinery. Cell Death Differ 5, 653–659.[CrossRef]
    [Google Scholar]
  17. Green, D. R. & Ware, C. F. ( 1997; ). Fas-ligand: privilege and peril. Proc Natl Acad Sci U S A 94, 5986–5990.[CrossRef]
    [Google Scholar]
  18. Griffith, T. S. Yu, X., Herdorn, J. M., Green, D. R. & Ferguson, T. A. ( 1996; ). CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance. Immunity 5, 7–16.[CrossRef]
    [Google Scholar]
  19. Krzyzowska, M., Schollenberger, A., Skierski, J. & Niemialtowski, M. ( 2002; ). Apoptosis during ectromelia orthopoxvirus infection is DEVDase dependent: in vitro and in vivo studies. Microbes Infect 4, 599–611.[CrossRef]
    [Google Scholar]
  20. Marsden, V. S. & Strasser, A. ( 2003; ). Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. Annu Rev Immunol 21, 71–105.[CrossRef]
    [Google Scholar]
  21. Matsue, H., Kobayashi, H., Hosokawa, T., Akitaya, T. & Ohkawara, A. ( 1995; ). Keratinocytes constitutively express the Fas antigen that mediates apoptosis in IFN gamma-treated cultured keratinocytes. Arch Dermatol Res 287, 315–320.[CrossRef]
    [Google Scholar]
  22. McKenna, K. C. & Kapp, J. A. ( 2004; ). Ocular immune privilege and CTL tolerance. Immunol Res 29, 103–112.[CrossRef]
    [Google Scholar]
  23. Mohan, R. R., Liang, Q., Kim, W. J., Helena, M. C., Baerveldt, F. & Wilson, S. E. ( 1997; ). Apoptosis in the cornea: further characterization of Fas/Fas ligand system. Exp Eye Res 65, 575–589.[CrossRef]
    [Google Scholar]
  24. Mullbacher, A., Wallich, R., Moyer, R. W. & Simon, M. M. ( 1999; ). Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections. J Immunol 162, 7315–7321.
    [Google Scholar]
  25. Niemialtowski, M. G. & Rouse, B. T. ( 1992a; ). Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis. J Immunol 148, 1864–1870.
    [Google Scholar]
  26. Niemialtowski, M. R. & Rouse, B. T. ( 1992b; ). Phenotypic and functional studies on ocular T cells during herpetic infections of the eye. J Immunol 149, 3035–3039.
    [Google Scholar]
  27. Niemialtowski, M. G., Spohr de Faundez, I., Gierynska, M., Malicka, E., Toka, F. N., Schollenberger, A. & Popis, A. ( 1994; ). The inflammatory and immune response to mousepox (infectious ectromelia) virus. Acta Virol 38, 299–307.
    [Google Scholar]
  28. Saraiva, M. & Alcami, A. ( 2001; ). CrmE, a novel soluble tumor necrosis factor receptor encoded by poxviruses. J Virol 75, 226–233.[CrossRef]
    [Google Scholar]
  29. Sayama, K., Yonehara, S., Watanabe, Y. & Miki, Y. ( 1994; ). Expression of Fas antigen on keratinocytes in vivo and induction of apoptosis in cultured keratinocytes. J Invest Dermatol 103, 330–334.[CrossRef]
    [Google Scholar]
  30. Smith, V. P. & Alcami, A. ( 2000; ). Expression of secreted cytokine and chemokine inhibitors by ectromelia virus. J Virol 74, 8460–8471.[CrossRef]
    [Google Scholar]
  31. Smith, V. P. & Alcami, A. ( 2002; ). Inhibition of interferons by ectromelia virus. J Virol 76, 1124–1134.[CrossRef]
    [Google Scholar]
  32. Smith, V. P., Bryant, N. A. & Alcami, A. ( 2000; ). Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins. J Gen Virol 81, 1223–1230.
    [Google Scholar]
  33. Streilein, J. W. ( 2003; ). Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 3, 879–889.[CrossRef]
    [Google Scholar]
  34. Streilein, J. W. & Stein-Streilein, J. ( 2000; ). Does innate immune privilege exist? J Leukoc Biol 67, 479–487.
    [Google Scholar]
  35. Toka, F. N., Niemialtowski, M. G., Spohr de Faundez, I. & Gierynska, M. ( 1996; ). Cytotoxic T lymphocyte control during ectromelia (mousepox) virus infection: interaction between MHC-restricted cells analyzed by non-radioactive fluorometry. Acta Virol 40, 239–244.
    [Google Scholar]
  36. Turner, S. J., Silke, J., Kenshole, B. & Ruby, J. ( 2000; ). Characterization of the ectromelia virus serpin, SPI-2. J Gen Virol 81, 2425–2430.
    [Google Scholar]
  37. Wilson, S. E., Li, Q., Weng, J., Barry-Lane, P. A., Jester, J. V., Liang, Q. & Wordinger, R. J. ( 1996; ). The Fas-Fas ligand system and other modulators of apoptosis in the cornea. Invest Ophthalmol Vis Sci 37, 1582–1592.
    [Google Scholar]
  38. Wilson, S. E., Pedroza, L., Beuerman, R. & Hill, J. M. ( 1997; ). Herpes simplex virus type-1 infection of corneal epithelial cells induces apoptosis of the underlying keratocytes. Exp Eye Res 64, 775–779.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80709-0
Loading
/content/journal/jgv/10.1099/vir.0.80709-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error