Alimentary TractPolarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells☆,☆☆
Section snippets
Cell lines and human IECs
Human carcinoma cell lines T84 and HT-29 were obtained from American Type Culture Collection (Rockville, MD). T84 cells were grown in Dulbecco's modified Eagle medium supplemented with 10% (vol/vol) fetal bovine serum (Hyclone, Logan, UT), 20 mmol/L supplemental glutamine, nonessential amino acids, and penicillin/streptomycin. HT-29 cells were grown under undifferentiated conditions in McCoy's media supplemented as above. The Epstein–Barr virus (EBV)-immortalized B lymphocyte cell line (B-LCL)
CD58 is constitutively expressed on the surface of human IECs
We showed in previous experiments that T84 and HT-29 cells engineered to express HLA-DRB1*0401 using recombinant retroviruses were able to stimulate normal, human CD4+ T-cell clones in an antigen-specific, HLA-restricted manner.4 Because these T-cell clones typically require a “costimulatory” signal (signal 2) from the APC in addition to the signal from the class II peptide complex (signal 1), the ability of the IEC lines to vigorously stimulate these clones suggested that they expressed a
Discussion
IECs are exposed to a high concentration of foreign antigens and are in intimate contact with various populations of T lymphocytes, both within the epithelium and in the underlying lamina propria. In this study, we show the constitutive expression of a functional T-cell costimulatory molecule, CD58, on the basolateral surface of human IECs. These data strengthen the supposition that IECs may participate in the initiation and/or regulation of mucosal T-cell responses.
Acknowledgements
The authors thank Susan Masewicz for assistance in generating the human T-cell reagents and for critical review of the manuscript; Adel Youakim for help with confocal microscopy; Jerry Nepom and Steve Ziegler for helpful comments; and Nicky Ducommun for help with the preparation of the manuscript.
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2021, Cell ReportsCitation Excerpt :IEC-derived MHC class II might influence mucosal immunity through canonical direct interaction with T cells. While in vivo evidence is sparse, studies with lung epithelia and many in vitro studies using T cells and gut-derived cell lines or organoids provide support for this potential mechanism (Framson et al., 1999; Dotan et al., 2007; Koyama et al., 2019; Rogoz et al., 2015; Westendorf et al., 2009; Biton et al., 2018). While the degree of direct contact of lamina propria T cells with IECs in vivo may limit this mechanism, it has been suggested that T cell interaction with Lgr5+ IECs can feed back and shape the differentiation of epithelial cells, thereby further impacting mucosal homeostasis (Biton et al., 2018).
Role of Epithelial Cells in Antigen Presentation
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2007, Mutation Research - Fundamental and Molecular Mechanisms of MutagenesisThe role of enterocytes in the intestinal barrier function and antigen uptake
2005, Microbes and InfectionCitation Excerpt :This contrasts with peripheral blood T cells, which are predominantly activated in an antigen-specific way via the TCR/CD3 complex. As a consequence, the signaling via CD58 on enterocytes may be relevant for these lamina propria T cells in the intestinal mucosa [80]. Although epithelial cell lines have been shown to be good targets for class I-restricted virus-specific cytotoxic T lymphocytes (CTL), they fail to prime an antiviral CTL response [64].
Intestinal epithelial cells secrete exosome-like vesicles
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Address requests for reprints to: Robert M. Hershberg, M.D., Ph.D., Virginia Mason Research Center, 1000 Seneca Street, Seattle, Washington 98101-2744. e-mail: [email protected]; fax: (206) 223-7638.
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Supported by a First Award from the Crohn's and Colitis Foundation of America.