MCP-1 derived from stromal keratocyte induces corneal infiltration of CD4+ T cells in herpetic stromal keratitis

Mol Cells. 2008 Jul 31;26(1):67-73. Epub 2008 Jul 2.


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. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Movement
  • Cells, Cultured
  • Chemokine CCL1 / genetics
  • Chemokine CCL1 / metabolism
  • Chemokine CCL2 / physiology*
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Chemokines / genetics
  • Chemokines / metabolism
  • Corneal Stroma / immunology*
  • Corneal Stroma / virology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium, Corneal / cytology
  • Epithelium, Corneal / metabolism
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Flow Cytometry
  • Herpesvirus 1, Human / physiology
  • Humans
  • Immunoenzyme Techniques
  • Keratitis, Herpetic / immunology*
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Ccl1 protein, mouse
  • Ccl2 protein, mouse
  • Chemokine CCL1
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokines
  • Cytokines
  • RNA, Messenger
  • Receptors, Chemokine