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Updated: Jun 26, 2026
Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
Published on: June 24, 2019
Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the
Ellen C Ebert1, Asit Panja, Rajalakshmi Praveen
1University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. ebertec@umdnj.edu
Insights
Human intestinal lymphocytes (IELs) and epithelial cells (ECs) synergistically increase IL-8 production through CD2-CD58 interaction. This cross-talk involves TNF-alpha and impacts gut immune responses.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Human intestinal CD3+TCRalphabeta+CD8+ intraepithelial lymphocytes (IELs) interact with epithelial cells (ECs) via CD103-E-cadherin.
- The functional consequences of this IEL-EC interaction remain largely uncharacterized.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying functional cross-talk between IELs and ECs.
- To identify key signaling pathways and cell surface molecules involved in IEL-EC communication.
Main Methods:
- Co-culture of IELs with HT-29 cells (model ECs) to assess Interleukin-8 (IL-8) production.
- Utilized Transwell assays to determine the requirement for cell contact.
- Investigated the role of specific cell surface molecules (CD2, CD58) and cytokine neutralization (TNF-alpha, IFN-gamma).
- Analyzed intracellular signaling pathways including p38 and JNK phosphorylation.
Main Results:
- IEL-EC co-culture resulted in synergistic IL-8 production, dependent on active transcription and cell contact.
- IL-8 release was specifically mediated by the CD2-CD58 interaction between IELs and ECs.
- Tumor necrosis factor-alpha (TNF-alpha) neutralization increased IL-8 production, while interferon-gamma (IFN-gamma) reduced IEL-derived IL-8.
- Both cell types utilized p38 and JNK phosphorylation for IL-8 production.
Conclusions:
- Synergistic IL-8 synthesis between IELs and ECs is initiated by CD2-CD58 engagement on IELs.
- This interaction triggers TNF-alpha release, which subsequently enhances IL-8 synthesis and CD58 expression by ECs.
- The findings reveal a novel mechanism of IEL-EC communication crucial for intestinal immune regulation.
Abstract:
Human intestinal CD3+TCRalphabeta+CD8+ intraepithelial lymphocytes (IELs) are intimately associated with epithelial cells (ECs) through binding of CD103 to E-cadherin. How these two cell types functionally interact is largely unknown. IEL-EC cross talk was determined using HT-29 cells as the model EC and IL-8 as the readout. IL-8 was derived from both cell types and synergistically increased when the cells were combined. This synergistic effect required active transcription by both IELs and HT-29 cells. Cell contact was required as shown by the loss of the synergistic increase in IL-8 when the two cell types were separated by Transwells. Specifically, IL-8 release required the binding of CD2 on the IELs to CD58 on the HT-29 cells. The association of the CD3/TCR complex with major histocompatibility antigen class I antigens was not involved. Antibody neutralization of tumor necrosis factor-alpha (TNF-alpha), but not interferon-gamma (IFN-gamma), resulted in increased IL-8 production by the coculture. Although both TNF-alpha and IFN-gamma increased IL-8 synthesis and CD58 expression by the HT-29 cells, only IFN-gamma reduced IL-8 production by IELs. IL-8 production by either cell type involved phosphorylation of p38 and JNK. In summary, the synergistic synthesis of IL-8 occurs when IELs are stimulated through the CD2 pathway by CD58 on HT-29 cells, resulting in TNF-alpha release that, in turn, augments IL-8 synthesis and CD58 expression by the HT-29 cells.
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