Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the CD2-CD58 interaction.
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.
Ebert
Ellen C
EC
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. ebertec@umdnj.edu
Panja
Asit
A
Praveen
Rajalakshmi
R
D018801:CD2 Antigens / Q000378:metabolism*; D018968:CD58 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018801:CD2 Antigens; D018968:CD58 Antigens; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma