Disclosed are methods of preparing multi-cellular three-dimensional tissue constructs, that include fibroblasts, endothelial cells, lymphocytes and epithelial cells. The present methods may include embedding fibroblasts and endothelial cells in a matrix enriched with gut basement membrane proteins to form a cell containing matrix that is then added to a bioreactor and exposed to epithelial cells and activated lymphocytes as the cell cultures. Also provided are the tissue constructs formed from such methods, a matrix enriched with gut basement membrane proteins and kits that include the same. Further provided are methods of measuring toxicity of a pathogen or commensal organisms, chemosensitivity of tissues to a toxic material and inflammatory conditions, which use the present multi-cellular three-dimensional tissue constructs.