Phenotypic and functional characterization of human TCR gamma delta+ intestinal intraepithelial lymphocytes

Intestinal intraepithelial lymphocytes (IEL) appear to represent a peculiar set of immune cells compartmentalized at the interface between the organism and the external environment. In previous studies we observed that within human IEL TCR-tau/delta T cells represent a major fraction that predominantly express the CD8 molecule and preferentially uses the V-delta-1 gene segment. Thus these data suggested a preferential accumulation/homing of CD8+ V-delta-1+ IEL within the human intestinal epithelium. However, to date the functional role of these cells with regard to immune regulation at this most critical immunological site is poorly understood. In this study, the cytotoxic potential and proliferative capacity of human IEL in response to mitogenic stimuli has been characterized with respect to IEL T cell receptor type and TCR-tau/delta variable gene segment usage as determined by flowmetry. The frequency of TCR-1+ IEL expressing both CD56 and CD16 which are considered to be NK-cell markers was found to be much higher (38.9 +/- 12.4%) than within intestinal lamina propria lymphocytes (LPL) (9.1 +/- 4.8%) or peripheral blood lymphocytes (PBL) (6.4 +/- 3.3%). In contrast, the fractions of CD16-CD56+ cells within IEL, LPL and PBL were comparable. Surprisingly, IEL mediated NK-cell activity (K562 lysis) was virtually absent whereas within PBL it was within the normal range. Furthermore, in cytotoxicity assays employing 51Cr-labeled OKT3 hybridoma cells and P815 cells as targets, the cytotoxic potential of IEL was much lower than that of PBL.(ABSTRACT TRUNCATED AT 250 WORDS)