HUMAN INTESTINAL EPITHELIAL-CELL LINES PRODUCE FACTOR(S) THAT INHIBITCD3-MEDIATED T-LYMPHOCYTE PROLIFERATION

Peripheral blood T lymphocytes (PET) proliferate more to anti-CD3 stim ulation than to anti-CD2 stimulation. On the other hand, fresh, but no t cultivated, intestinal intraepithelial lypmphocytes (iIEL) exhibit a lower response to CD3 stimulation in comparison to CD2. The goal of t his study was to show that the anti-CD3 T-cell response depends on the microenvironment and is independent of the origin of the lymphocytes. Cultured T-cell lines were stimulated with either an anti-CD3 mAb or an anti-CD2 mAb. Either conditioned supernatant from intestinal epithe lial cell (IEC) lines or non-conditioned medium (negative control) was added. After 2 days cytokine production and proliferation were measur ed. Conditioned supernatant decreased the proliferative response of sm all and large bowel iIEL compared to controls (P = 0.04). In the same experiments, the cytokine production was non-significantly decreased. Immortalized iIEL, that are not regularly stimulated by their CD3 path way, showed a similar decrease in proliferation (P < 0.001) and cytoki ne production (P = 0.01) when incubated with conditioned supernatant. Similar results were also obtained with a non-immortalized and an immo rtalized PET line (P < 0.001). In a small bowel iIEL cell line, that e xhibited a significant response to anti-CD2 stimulation, the prolifera tive response to anti-CD2 stimulation was preserved, Active conditione d supernatant could be generated from three independent IEC lines and a liver derived epithelial cell line, but not from a non-epithelial co ntrol cell line or two extraintestinal epithelial cell lines. We concl ude that supernatants of cultured IEC contain soluble factor(s) that c ause cultured iIEL and extraintestinal lymphocytes to behave like fres h iIEL, These results, therefore, support and extend the studies of ot hers which suggest that the intestinal microenvironment mucosalizes ly mphocytes. (C) 1997 Elsevier Science B.V.