Characterisation and functional properties of human colonic intra-epithelial lymphocytes
(1997)
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- IEL are a unique population of cells. Their function remains largely unknown. Human colonic IEL were therefore isolated in order to characterise their phenotype and to perform functional assays. <BR> The isolated IEL population has a phenotypic distribution (95% CD3, ± 80% CD8) similar to that seen in tissue section. Thus IEL appear to be a T cell CD3+CD2+CD8 but CD5 (a pan T cell marker) expression by IEL appeared to be altered. IEL are predominantly memory cells, express conventional T cell activation markers IL-2R (CD25) and class II HLA antigens. The high percentage of cells expressing IL-2R and HLA-DR in our study presumably reflects the sensitivity of flow cytometry. Our study has shown that natural killer cells were a minority population in IEL as reported by others but that non-MCH-restricted cytotoxic T cells were present. The majority of human IEL use the TCR αβ. However, in the large bowel, about 20% of IEL are TCR1 (γδ). Furthermore, a statistically significant increase in the proportion of TCR1 in IBD patients compared with controls was shown. The IEL population contains virtually no B cells and no macrophages. They have little proliferative capacity following stimulation with PHA. <BR> The intimate anatomical relationship between IEL and intestinal epithelial cells suggests that the function of one is affected by the other in a manner that may have important pathophysiological significances. Furthermore, enhanced epithelial MHC class II expression could facilitate the presentation of autoantigens to T lymphocytes, resulting in an exaggerates or inappropriate inflammatory response. We have confirmed “at the mucosal level” that colonic epithelial cells are able to activate IEL dependent on their expression of HLA molecules. <BR> a logical step forward was therefore to study the putative suppressive activity of IEL. We have shown that human colonic IEL have a potent down-regulatory effect on lectin-driven proliferation of autologous lamina propria cells in control and IBD suibjects. The effect is CD-8 dependent, γδ independent and mediated by a soluble factor. IEL also specifically down-regulated total immunoglobulin synthesis and IgA by autologous lamina propria cells. Further strudies using an antigen-driven system have shown that there many be a defect in this down-regulatory function of IEL in IBD to various antigens. <BR> It is likely that some of the immunoregulatory effects described above were caused by cytokines produced by the IEL. Many different cytokines are produced during an immune system and also affect the function of non immune cells such as epithelial cells. Indeed, we have shown that colonic IEL are able to produce cytokines, eg IL-2, interferon-γ and IL-10. IEL can enhance the PHA-induced synthesis of IL-2 and interferon-γ by lamina propria tissues as well as i the epithelium. Indeed, sufficient quantify of cytokines are produced by IEL to induce class II molecules on HT-29. <BR> IEL)s role in host defence as cytolytic cells is under active study. This function is suggested by their location, their morphological appearance and some phenotypical evidence. Unlike in the mouse, the evidence for a cytotoxic function of human IEL remains scanty. However, recent studies have shown that IEL are capable of some cytottoxic activity under particular circumstances. Our own data suggest that, in contrast to LPMNC, human colonic IEL do not exhibit MHC-restricted T cell cytotoxicity
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Hoang, P. (1997). Characterisation and functional properties of human colonic intra-epithelial lymphocytes. https://hdl.handle.net/2078.5/111413