008665��0.002790) (Figure 8). Figure 8 MAdCAM-1 mRNA expression selleck Sunitinib is similar in BE and duodenal tissue from BE patients and controls. Discussion This is the first study showing that the T-cell composition in tissue from BE (epithelium and lamina propria) is similar to what is found in duodenal tissue from BE and controls. As the specialized intestinal epithelium in BE esophagus is to a large extent similar to epithelium normally found in the duodenum, this suggests that the immune cell composition observed in BE is not an indication of an active Th2 type inflammation, as has been suggested before [7], [11], but rather a consequence of metaplastic intestinal-type changes that have occurred in BE.
The morphology of eosinophils in BE and duodenum [16], [17] exhibited a similar non-polarized, not-activated phenotype, which is in contrast to eosinophils found in allergic disorders that are polarized with the presence of free granules [18], [19]. This finding is the first indication that immune cells in BE are similar to those normally found in intestinal tissue and that their presence is likely not to be a consequence of inflammation. The observed slight difference in numbers of eosinophils in BE and duodenum may be explained by an aberrant intestinal microenvironment and/or a the known less well developed vasculature in BE [20], [21]. The high numbers of lymphocytes in BE were previously interpreted as evidence of an inflammatory response [7], [11]. However, little data are available regarding the specific phenotypes of these T-cells because of the limited analytic power of IHC to do this.
Therefore, we applied a novel technique to expand ex vivo T-cells to analyze T-cell phenotypes by multicolor FACS analysis. Comparing this technique with IHC stainings showed similar numbers of CD3+/CD4+ and CD3+/CD8+-cells (Figures 2 and and33). In our study, similarly high percentages of memory CD4+-cells were observed in ex vivo cultures of duodenum and BE. It is known that a healthy duodenum has abundant lymphocytes [22]. The homing of these cells to this tissue is mediated by a large repertoire of gut homing signals such as specific chemokines and chemokine receptors [23]. This coincides with the proximity of mesenteric lymph nodes and Peyer’s patches [24]�C[26]. The absolute numbers of lymphocytes in BE were lower than found in the duodenum.
The underlying mechanism remains to be elucidated, but structural differences between BE and duodenal tissue might well be involved, for example, as suggested above, a more extensive vasculature in the duodenum compared to BE tissue that may facilitate lymphocyte homing to intestinal tissue [16], [20]. In addition, homing of T-cells from Peyer’s patches towards the submucosa may increase the numbers of T-cells found in the duodenum [12], [23]. Carfilzomib Despite the 2.5 fold difference in absolute numbers, the relative numbers of CD3+/CD4+ and CD3+/CD8+-cells in BE were similar as found in duodenum (Figure 2).