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The Changes Of TGF-β1-secreting Activities Of Murine Intestinal Intraepithelial Lymphocytes In The Model Of Stress Ulcer

Posted on:2006-02-09Degree:MasterType:Thesis
Country:ChinaCandidate:G F CaoFull Text:PDF
GTID:2144360152996756Subject:Immunology
Abstract/Summary:PDF Full Text Request
PrefaceIntraepithelial lymphocytes (IELs) are widely distributed in the epithelial of skin, respiratory tract, digestive tract and genitourinary tract. Intestinal intraepithelial lymphocytes (iIEL)are a subset of lymphocytes located among the intestinal intraepithelial cells (IEC ). As a special subset of lymphocyte groups, iIEL often contact with the intestinal normal flora and pathogens. Subsets of iIEL have been shown to play a role in the prevention of the infection, the regulation of epithelial cell function and the regulation of immune response to foreign antigen. Studies on iIEL ,conducted in the middle of 1980s,showed that there were significant differences in phenotype, subsets with iIEL and conventional T lymphocytes found in the thymus spleen, lymph nodes and peripheral blood. Therefore, many scholars have focused on the development site of iIEL. More and more evidences indicate that there exists an extrathymus development route of CD8ααiIEL in the intestinal epithelium. With all these achievements, we still know little about the physiological functions of iIEL, especially their development mechanism, how the IECs present antigens and their relationship with digestive disease and oral tolerance. It is up to further studies and discussions.Peptic ulcer is a common disease over the world. It has been proved by many experiments and clinical observations that peptic ulcer is related to delirium and stress. Up till now, not much is known about the iIEL biology activity under stress. In recent years, our laboratory have taken a series of studies concerning the influences of stress stimuli on the biological functions of iIEL. We have observed the variation in characteristics of iIEL and its subgroups followingwater - immersion induced stress and these include, the number, cytolytic activity to kill target cells (such as tumor cells) and secretory activity of TH1,TH2 cytokines. Our result showed that the decline in total number of iIEL , TCRαβT/ TCRγδT is also declined, and relative higher number of TCRγδT subgroup, secretory activity of TH, cytokines(IL -2,TFN -7) is increased; secretory activity of TH2 cytokines (IL -4) has not change. With all achievements, iIEL could enhance the cellular immunity to clear amounts of death cells in order to maintain immunologic homeostasis. In the same time, iIEL could also promote the differentiation and proliferation of epithelial cells and concrescence of ulcer.Transforming growth factor beta(TGF -β) is one of multifunctional cytokines. Some scholars reported; there are mainly 3 kinds TGF - β, but TGF - β1 is most important.Under the stress condition, it is still unknown of TGF - β1 cytokine secretion of iIEL. To study and research the biological activity of iIEL to stress, in this report, studies were undertaken about the level of TGF - β1 cytokine - secreting of iIEL in the stress induced ulcer models, in order to detect whether the TGF - β1 secretion varies in iIEL. And then it further clarifies the biological function of iIEL in the process of formation and concrescence of ulcer.Materials and MethodsIn this article, C57BL/6(B6) mice were divided randomly into 6 groups, 5 of which served as experimental groups, the other one served as control group. Stress ulcer was induced by water - immersion restraint stress in the experimental groups, iIEL from which were isolated on day the 1st, 2nd, 3rd, 4th and 5th after stress. iIEL from the control group were prepared without stress. Culture su-pernatants of iIEL from these groups were collected. The TGF - β1 concentrations in the culture supernatants of iIEL were detected with ELISA kit.DiscussionAs a special subset of lymphocyte groups, iIEL often make contact with theintestinal normal flora and pathogens. Subsets of iIEL have been shown to play a role in the prevention of the infection, the regulation of epithelial cell functions and the regulation of immune response to foreign antigen. In recent years, with the aid of National Natural Science Fund project, our laboratory have taken a series of studies concerning the influences of stress stimuli on the biological functions of iIEL. We have observed the variation in characteristics of iIEL and its subgroups following water - immersion induced stress and these include, the number, cytolytic activity to kill target cells ( such as tumor cells) and secretory activity of TH1,TH2 cytokines. Our result showed that the decline in total number of iIEL , TCRαβT/ TCRγδT is also declined, and relative higher number of TCRγδT subgroup, secretory activity of TH1 cytokines(IL -2,TFN -γ) is increased; secretory activity of TH2 cytokines (IL -4) has not change. With all a-chievements, iIEL could enhance the cellular immunity to clear amounts of death cells in order to maintain immunologic homeostasis. In the same time, iIEL could also promote the differentiation and proliferation of epithelial cells and concrescence of ulcer.Result from our former study showed that no significant changes was found in TNF - a - secreting activity of iIEL in the time span we examed after ulcer occurred. In addition, the culture supernatants of iIEL were found to demonstrate marked promoting effects on the proliferation of L929 cell. Therefore, we propose that TGF - β1 - like substances may exist in the supernatant of iIEL culture in the early stage of stress ulcer. Therefore, we examined the level of TGF - β1 in the 1 -5 days after stress. The result showed that a temporary elevation in TGF - β1 - secreting level in mice iIEL after stress ulcer was induced by receiving water - immersion restraint stress, which demonstrated that, iIEL may exert a significant effect on the restoration of mucosa immune function and the renewal of intestine epithelium by up - regulation TGF - β1. The significations of up - regulation TGF - β1 are as follows: (1) TGF - β1 is related with promoting the proliferation of mucosa epithelium in stress ulcer. (2) TGF - β1 is related with no significant changes of the TNF - α - secreting level in stress ulcer. (3) TGF - β1 is related with promoting IgA in stress ulcer.In conclusion, the enhanced immunoactivity of iIEL from stress ulcer was...
Keywords/Search Tags:Intestinal intraepithelial lymphocytes (iIEL), stress, TGF - β1
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