Intraepithelial lymphocytes

Intraepithelial lymphocytes (IF.Ls) reside between intestinal epithelial cells and are the first cells to contact luminal antigen that crosses the mucosa in an M cell-independent manner. This heterogeneous population of mainly T cells comprises a very large number of cells (more than half the number of T cells in peripheral organs) but their function remains poorly understood. The majority of murine IELs (80%) arc CD3+, and over 75% of these also express CDS. In mice and chickens, significant numbers of yS TCR' IELs are found (40-60%) in addition to a(3 TCR+ cells; however, this number varies with mouse strain, age and housing conditions. The y8 TCR4 IELs represent a minor component of human IELs (-15%) under normal conditions, but significantly increase under certain conditions, such as celiac disease.

The physiological role of IELs is poorly understood; however, several functions for these cells have been described and this diversity is consistent with their phenotypic heterogeneity. IELs have been shown to mediate antigen-specific delayed-type hypersensitivity (DTH) responses, to exhibit virus-specific CTL function, to express natural killer (NK)-like activity and to produce a local graft-versus-host reaction (GVHR) when transferred to semiallogeneic hosts. IELs respond poorly to conventional T cell mitogens when compared to splenic T cells; however, there is evidence that human IELs are induced to proliferate via a CD2 pathway rather than through stimulation of the CD3-TCR complex. With regard to regulation of humoral immunity, y8 TCRf IEL T

cells have been shown to abrogate the induction of mucosal tolerance, while a(3 TCR IEL T cells provide help for production of IgA. Interestingly, the targeted disruption of the 8 chain of TCR in mice results in a lack of y8 T cells among IELs and in a mucosal IgA deficiency, suggesting that y8 T cells may upreg-ulate CD4+ T helper cells for mucosal immunity. IELs can be induced to produce a variety of cytokines which are characteristically produced by Tnl- and TH2-type cells and a(3 TCR4 IELs can also provide help for B cell responses.

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