MORPHOLOGICAL, PHENOTYPIC AND FUNCTIONAL-CHARACTERISTICS OF A PURE POPULATION OF CD56- CD3- LARGE GRANULAR LYMPHOCYTES GENERATED FROM HUMANDUODENAL MUCOSA( CD16)

Interleukin-2 (IL-2)-dependent large granular lymphocytes (LGL) with a distinctive surface phenotype were generated from histologically norm al duodenal biopsy tissues. Immunoperoxidase staining of the mucosa wi th an anti-CD56 monoclonal antibody revealed LGL localized in the lami na propria rather than in the epithelium. Light and electron microscop y demonstrated azurophilic and electron-dense cytoplasmic granules. Fl ow cytometry analysis revealed that these cells express CD45, CD56, CD 2, CD7, CD11a, CD18, CD69 and the intermediate affinity (p70) IL-2 rec eptor (IL-2R) but not CD57, CD16, CD3, CD4, CD5, CD8, CD45RA, CD25, or the high affinity p55 IL-2R. The LGL proliferated when cultured in th e presence of human rIL-2 but not in the presence of human rIL-4. Func tional studies demonstrated that the LGL had strong cytotoxicity again st natural killer (NK) target cells, K562, but not NK-resistant target s such as Colo 205, Melanoma and Epstein-Barr virus (EBV)-transformed B-cell lines. The LGL expressed genes for IL-5, IL-8, granulocyte-macr ophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-a lpha (TNF-alpha) and the corresponding cytokines were detected in cult ure supernatant. These results provide evidence for an important role of gut mucosal LGL in the induction and regulation of inflammation and immunity in the gut.