Our in vitro studies further confirmed that CD94 induction was selective because CD94, but not the additional NK receptors tested (such as CD16 and CD56, data not shown), could be induced on CD8+ T-IELs upon TCR and IL-15 activation. induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. Conclusions: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-ECspecific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion. GASTROENTEROLOGY 2000;118:867-879 (n = PS-1145 4) 0.001) as well as with adults (40 16 vs. 10 7; 0.001). Open in a separate window Fig. 2 Development of CD94+ IELs is definitely celiac disease specific and is associated with disease activity. Immunoperoxidase staining using anti-CD94 antibody was performed on freezing sections of duodenum in (and 0.001) compared with settings with normal intestine, settings with villous atrophy unrelated to celiac disease, or individuals receiving GFD. ( 0.001) (Fig. 3, Fig. 3). Additional settings included biopsy specimens from 2 children, 1 with Crohn’s disease and 1 with autoimmune enteropathy, that also showed normal frequencies of CD94+ IELs (22% and 18%, respectively; data not demonstrated). The frequencies of CD94+ IELs in control biopsy specimens without villous atrophy and in biopsy specimens from individuals on GFD were similar to that observed in IELs isolated from medical samples (23% 9% [n = 3] vs. 27% 10% [n=15]; Table 1 and Number 3B). Despite a designated relative increase of CD94+ IELs in active celiac disease, the percentage of IELs PS-1145 expressing additional NK receptors was within the normal range (Table 2). Table 2 Comparison between the expression of CD94 and additional NK receptors by IELs in active celiac disease (n = 15)27 11indicate areas of strong positivity for IL-15. Conversation We show with this study that most normal human being T-IELs communicate at least 1 NK receptor and that the TCR+ IELs that increase in untreated celiac disease specifically and selectively communicate the NK receptor CD94. We also provide practical evidence that improved expression of CD94 in active celiac disease may be the consequence of local launch of IL-15, a potent cytokine produced in situ by intestinal ECs and triggered macrophages (examined by Waldmann and Tagaya51) and/or Rabbit Polyclonal to MARK2 direct TCR activation. T cells that communicate numerous receptors of the NK lineage have been reported in mice and humans, in normal as well as with pathological claims.23, 52, 53, 54, 55, 56, 57, 58, 59 NK receptor manifestation may be portion of a genetic system of differentiation, 52 or alternatively it may be imparted on activation of mature T cells.50, 60 In the present study we confirmed the manifestation of CD56 and CD94 by 7% and 27% T-IELs, respectively, and the paucity of CD16 expression, while previously reported on T-IELs.22, 24 We determined for the first time the pattern of manifestation of an extended set of NK receptors by T-IELs and compared it with that of T-PBLs. The results showed that IELs and PBLs markedly differed in the rate of recurrence of T cells expressing NK receptors as well as in the nature of the NK receptors indicated. Thus, more than 60% of T-IELs vs. only 20%C30% of T-PBLs indicated at least 1 NK receptor. NKR-P1A was PS-1145 indicated on a much larger subset of T-IELs than T-PBLs, and Pen5 and NKp46 were indicated by a subset of T-IELs but not by T-PBLs. Conversely, CD57 was indicated by a subset of T-PBLs but not by T-IELs. These NK receptorCexpressing T-IELs, or a subset of them, might be the counterpart to the mouse NK receptorCexpressing T-IELs, which are thought to differentiate in the gut wall and increase in response to self antigens.29, 61, 62 Alternatively, the expression of NK receptors on human T-IELs could be the consequence of particular activation events. In any case, our data suggest that the gut epithelium is definitely a unique environment that favors the differentiation and/or development of particular subsets of NK receptorCexpressing T cells in humans as well as with mice. Some NK receptors, such as CD16, endow T-IELs with NK-like PS-1145 properties23 that may contribute to the innate defense of the intestinal epithelium.25, 26, 27, 28 Other NK receptors, such as.