Mesenchymal cells stimulate human intestinal intraepithelial lymphocytes.
OBJECTIVE
Intraepithelial lymphocytes (IELs) from human intestinal mucosa proliferate minimally to T-cell stimuli. Optimal growth may depend on factors that are missing in vitro, such as accessory cells. The aim of this study was to determine whether mesenchymal cells costimulate IELs.


METHODS
IELs were isolated from human jejunum and cultured with fibroblasts or smooth muscle cells (mesenchymal cell models for mucosal myofibroblasts) and various T-cell stimuli. Proliferation was determined by [3H]thymidine incorporation, and interleukin 2 (IL-2) production was measured by enzyme-linked immunosorbent assay. Surface molecules were detected by immunofluorescence and flow cytometry.


RESULTS
The proliferative responses of IELs to mitogen (phytohemagglutinin), superantigen (staphylococcal enterotoxin B), or anti-CD3 antibody were increased greatly by coculture with mesenchymal cells, while only slightly by peripheral-blood monocytes, the classical antigen-presenting 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 alpha4beta1 (very late activation 4[VLA-4]) and major histocompatibility complex (MHC) class I, as their respective antibodies blocked the 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 likely serve this role.
Roberts
A I
AI
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Nadler
S C
SC
Ebert
E C
EC
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology*; D007583:Jejunum / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000502:physiology
D015395:Histocompatibility Antigens Class I; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen