Mesenchymal cells stimulate human intestinal intraepithelial lymphocytes

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Intraepithelial lymphocytes (IELs) in human intestinal mucosa show limited proliferation to T-cell stimuli in vitro.
• Accessory cells may be crucial for optimal IEL growth, but are often absent in standard culture conditions.

Purpose of the Study:

• To investigate whether mesenchymal cells can costimulate IELs.
• To elucidate the mechanisms underlying mesenchymal cell-mediated IEL proliferation.

Main Methods:

• Human jejunal IELs were cultured with fibroblasts or smooth muscle cells (mesenchymal models).
• Proliferation was assessed via [3H]thymidine incorporation; IL-2 production by ELISA.
• Surface molecule expression was analyzed using immunofluorescence and flow cytometry.

Main Results:

• Mesenchymal cells greatly increased IEL proliferation and IL-2 production compared to peripheral blood monocytes.
• This costimulation required direct cell contact and was partially mediated by VLA-4 and MHC class I.
• B7, CD2, and MHC class II molecules were not involved in the observed costimulation.

Conclusions:

• Optimal growth of human IELs is dependent on contact with mesenchymal cells.
• This interaction is mediated by VLA-4 and MHC class I, suggesting a role for myofibroblasts in mucosal immunity.