MESENCHYMAL CELLS STIMULATE HUMAN INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

Background & Aims: Intraepithelial lymphocytes (IELs) from human intes tinal mucosa proliferate minimally to T-cell stimuli. Optimal growth m ay depend on factors that are missing in vitro, such as accessory cell s. The aim of this study was to determine whether mesenchymal cells co stimulate IELs. Methods: IELs were isolated from human jejunum and cul tured with fibroblasts or smooth muscle cells (mesenchyma cell models for mucosal myofibroblasts) and various T-cell stimuli. Proliferation was determined by [H-3]thymidine incorporations, and interleukin 2 (IL -2) production was measured by enzyme-linked immunosorbent assay. Surf ace molecules were detected by immunofluorescence and flow cytometry. Results: The proliferative responses of IELs to mitogen (phytohemagglu tinin), superantigen (staphylococcal enterotoxin B), or anti-CD3 antib ody were increased greatly by coculture with mesenchymal cells, while only slightly by peripheral-blood monocytes, the classical antigen-pre senting cells. IL-2 production and receptor expression also increased. Mesenchymal cell costimulation of IEL growth required direct contact between the two cell types and was partly dependent on the integrin al pha(4) beta(1) (very late activation 4[VLA-4]) and major histocompatib ility complex (MHC) class I, as their respective antibodies blocked th e effect. The surface molecules B7 (CD80), CD2, and MHC class II were not involved. Conclusions: Optimal IEL growth depends on their contact with mesenchymal cells, an interaction that is mediated by VLA-4 and MHC class I. In mucosal immunity, basement membrane myofibroblasts lik ely serve this role.