Do human Peyer's patches contribute to the intestinal intraepithelial gamma/delta T-cell population?

T-cell receptor gamma/delta+) (TcR gamma/delta+) lymphocytes in human Peyer's patches (PP) adjoining ileal mucosa were studied by monoclonal antibodies with paired immunofluorescence staining in situ and by flow-cytometric phenotyping of isolated cells. The proportion of gamma/delta+ T cells in the follicle-associated epithelium outside the M-cell areas (median 4.1%, range 2.2-30.1%) was similar to that in mucosal villous epithelium (median 4.4%, range 0.5-30.5%). Most intraepithelial gamma/delta cells (approximately 90%) expressed CD45R0 but only a few expressed CD8 (< 10%) and none L-selectin; a dominating subset (median 46%) employed the V delta 1/J delta 1 gene product (range 22-100%). The M-cell areas lacked gamma/delta cells but contained clustered CD20+ and CD3+ lymphocytes. The subepithelial PP dome area and interfollicular (T-cell) zones, as well as the mucosal lamina propria, contained very few gamma/delta cells (median 1.7%, range 0.4-8.9%) which were dominated (88-100%) by the V delta 2-encoded subset. Those in the dome area and lamina propria were often (approximately 75%) CD45R0+ (range 44-90%) while very few (approximately 2%) expressed L-selectin (range 0-15%). By contrast, CD45R0 expression on gamma/delta cells in the PP T-cell zones was relatively low (approximately 46%) and that of L-selectin relatively high (approximately 43%). In conclusion, TcR gamma/delta + cells are quite rare in human PP and belong mainly to the V delta 2-encoded subset, thus being different from most intraepithelial gamma/delta cells that probably have another origin. The L-selectin+ fraction of PP gamma/delta cells presumably represent newly recruited 'naive' T lymphocytes while CD45R0+ gamma/delta cells both in PP and lamina propria are probably antigen-primed.