Gastroenterology

Gastroenterology

Volume 116, Issue 5, May 1999, Pages 1054-1062
Gastroenterology

Alimentary Tract
Polarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells,☆☆

https://doi.org/10.1016/S0016-5085(99)70008-9Get rights and content

Abstract

Background & Aims: Intestinal epithelial cells (IECs) can process foreign protein antigens and display antigenic peptides to CD4+ T lymphocytes via HLA class II molecules. The purpose of this study was to determine the nature of the second, or costimulatory, signal provided by IECs. Methods: We investigated surface expression of the costimulatory molecules CD58 (LFA-3), CD80 (B7-1), and CD86 (B7-2) by using flow cytometry, confocal microscopy, and vectorial biotinylation. Antibodies specific for CD58, CD80, and CD86 were used in blocking experiments to assess the role of these molecules in providing a costimulatory signal to CD4+ T cells by IECs. Results: CD58, but not CD80 or CD86, was observed to be expressed constitutively on both native IECs and in the IEC lines T84 and HT-29. The surface expression of CD58 was highly polarized and restricted to the basolateral surface of the cell. Antibodies against CD58, but not CD80 or CD86, inhibited the stimulation of CD4+ T-cell proliferation mediated by IECs. Conclusions: CD58 is expressed by polarized IECs in a topologically restricted manner at the region of T-cell contact and can function as a costimulatory molecule in HLA class II–mediated antigen presentation.

GASTROENTEROLOGY 1999;116:1054-1062

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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    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.

    ☆☆

    Supported by a First Award from the Crohn's and Colitis Foundation of America.

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