Exclusive increase of CX3CR1+CD28−CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes
✍ Scribed by Taku Kobayashi; Susumu Okamoto; Yuko Iwakami; Atsushi Nakazawa; Tadakazu Hisamatsu; Hiroshi Chinen; Nobuhiko Kamada; Toshio Imai; Hidemi Goto; Toshifumi Hibi
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 584 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
Background:
Cx3cl1/fractalkine (fkn) has been reported to play important roles in various inflammatory diseases. we examined the role of fkn and its receptor cx3cr1 in t-cell migration in the inflammatory bowel diseases (ibds), ulcerative colitis (uc) and crohn's disease (cd).
Methods:
Cx3cr1 expression on peripheral cd4(+) cells from normal controls (nl n = 24) and ibd patients (uc n = 28, cd n = 26) was examined using flow cytometry. cx3cr1(+)cd4(+) t cells were further characterized for surface antigens, cytokine production, and cytotoxic granule release by flow cytometry and elisa. fkn expression in 53 colonic biopsy specimens (uc n = 20, cd n = 23, nl n = 10) was analyzed by quantitative pcr and immunohistochemistry. isolated lamina propria and intraepithelial lymphocytes were also analyzed by flow cytometry (uc n = 10, cd n = 10, nl n = 6).
Results:
Cx3cr1(+)cd4(+) cells were increased in ibd while they were virtually absent in controls. upregulation of cx3cr1 on cd4(+) t cells was positively correlated with disease activity. these unique t cells expressed markers for both effector memory and cytotoxic cells. interestingly, cx3cr1 was expressed on cd4(+) t cells lacking cd28. cx3cr1(+)cd28(-)cd4(+) cells produced more ifn-gamma and tnf-alpha than cx3cr1(-) counterparts and released cytotoxic granules. fkn mrna was upregulated in inflamed colonic tissues and robust expression of fkn was immunohistochemically observed on epithelial cells. although cx3cr1(+) cd4(+) cells could not be detected in the gut, cd28(-)cd4(+) cells were found in ibd mainly as intraepithelial lymphocytes.
Conclusions:
Fkn/cx3cr1 may contribute to the pathogenesis of ibd through the emergence of unique cx3cr1(+)cd28(-)cd4(+) t cells that can act both as proinflammatory and cytotoxic cells.