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Published on: April 21, 2015
Polarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells
P E Framson1, D H Cho, L Y Lee
1Virginia Mason Research Center, Seattle, USA.
Insights
Intestinal epithelial cells provide a costimulatory signal to T cells via CD58 (LFA-3), a molecule expressed on their basolateral surface. This finding is crucial for understanding immune responses in the gut.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Intestinal epithelial cells (IECs) process antigens and present peptides via HLA class II molecules to CD4(+) T cells.
- The nature of the costimulatory signal provided by IECs remained unclear.
Purpose of the Study:
- To identify the costimulatory molecules expressed by IECs.
- To determine the functional role of these molecules in T cell activation.
Main Methods:
- Investigated surface expression of CD58 (LFA-3), CD80 (B7-1), and CD86 (B7-2) on IECs using flow cytometry, confocal microscopy, and vectorial biotinylation.
- Utilized blocking antibodies against CD58, CD80, and CD86 to assess their role in CD4(+) T cell stimulation.
Main Results:
- CD58 was constitutively expressed on IECs, while CD80 and CD86 were not.
- CD58 expression was polarized to the basolateral surface of IECs.
- Blocking CD58, but not CD80 or CD86, inhibited IEC-mediated CD4(+) T cell proliferation.
Conclusions:
- CD58 is expressed by polarized IECs at the site of T cell contact.
- CD58 functions as a costimulatory molecule in HLA class II-mediated antigen presentation by IECs.
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.
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