MCP-1 derived from stromal keratocyte induces corneal infiltration of CD4+ T cells in herpetic stromal keratitis.
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.
Lee
Sun Kyoung
SK
The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Choi
Beom Kyu
BK
Kang
Woo Jin
WJ
Kim
Young Ho
YH
Park
Hye Young
HY
Kim
Kwang Hui
KH
Kwon
Byoung S
BS
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000502:physiology*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003319:Corneal Stroma / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C502258:Ccl1 protein, mouse; C491768:Ccl2 protein, mouse; D054402:Chemokine CCL1; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine