Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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MCP-1 Derived from Stromal Keratocyte Induces Corneal Infiltration of CD4+ T Cells in Herpetic Stromal Keratitis

  • Lee, Sun Kyoung (The Immunomodulation Research Center, University of Ulsan) ;
  • Choi, Beom Kyu (The Immunomodulation Research Center, University of Ulsan) ;
  • Kang, Woo Jin (The Immunomodulation Research Center, University of Ulsan) ;
  • Kim, Young Ho (The Immunomodulation Research Center, University of Ulsan) ;
  • Park, Hye Young (Department of Molecular Cell Biology Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University) ;
  • Kim, Kwang Hui (The Immunomodulation Research Center, University of Ulsan) ;
  • Kwon, Byoung S. (The Immunomodulation Research Center, University of Ulsan)
  • Received : 2007.11.21
  • Accepted : 2007.12.24
  • Published : 2008.07.31
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Abstract

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

Keywords

Acknowledgement

Supported by : US Public Health Service, Arthritis Foundation, Korea Science and Engineering Foundation, Ministry of Health and Welfare, National Cancer Center

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