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The Study On Active IL-16 Levels In Tuberculous And Malignant Pleural Effusion And The Mechanism Involved

Posted on:2012-04-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:L TianFull Text:PDF
GTID:1114330335954965Subject:Immunology
Abstract/Summary:PDF Full Text Request
IL-16 is a cytokine found as a ligand for CD4 and can chemoattract all CD4+ cells, especially CD4+T cells. Subsequent researches demonstrated cytokine IL-16 was not only chemokine, but also pro-inflammatory factor, in addition to inhibitory cytokine.Ⅰ. Increased IL-16 released in tuberculous pleural effusionIt was observed the concentration of IL-16 in tuberculous PE was significantly greater than that in malignant PE. ELISA was used to detect the concentration of secreted IL-16 in TBPE and MPE. It was found increased IL-16 released in tuberculous pleural effusion, in accordance with previous research. These results demonstrated that different or more pleural sources of IL-16 existed in tuberculous patients, or different expression levels despite same source.Ⅱ. The cell source of active IL-16 in pleural effusionPro-IL-16 is constitutively expressed in immune and non-immune cells. Lymphocytes, especially CD4+T cells, were dominant in pleural effusion. It was reported the absolute lymphocyte counts, especially CD4+T cells counts, displayed the highest values in tuberculous PE and showed a significant increase of CD4+T cells and decrease of CD8+T cells in camparison with that in malignant PE. To find out whether the increased CD4+T cells are the source of increased IL-16 in PE, FCM was used to evaluate IL-16(including pro-IL-16) protein expression in T cells(including CD3+CD8+T cells and CD3+CD8-T cells) and B cells.1. Cytokine IL-16 (including pro-IL-16) constitutively expressed in T cells and B cells both in blood and pleural effusion FCM was used to test the percentage of IL-16+cells in T cells and B cells from TB patients and Malignant patients. It was found IL-16 were almost constitutively expressed in all T cells (CD8+and CD8-) and a vast majority of B cells, not only in PB but also in PE.2. CD3+CD8- T cells were dominant in IL-16 positive cells in all situations.In the reversed orientation, the percentage of CD3+CD8-T cells, CD3+CD8+T cells and CD19+B cells in IL-16 positive cells were also analysed. Data demonstrated CD3+CD8-T cells were dominant in IL-16 positive cells in all situation, followed by CD3+CD8+T cells.3. The MFI of IL-16 in T cells is much higher than in B cellsThe average IL-16 protein expressions in IL-16+T cells (including CD3+CD8+T cells and CD3+CD8-T cells) showed obviously greater values in comparison with those in IL-16+B cells from tuberculous and malignant pleural effusion.The protein amounts of IL-16 were much greater in CD3+CD8-IL-16+T cells than those in CD19+IL-16+B cells in Tuberculous and malignant blood.For single cell, T cell expressed more IL-16 proteins.4. Different IL-16 secretion abilities of CD4+T cells and CD8+T cells in Tuberculous group and malignant groupThe mean bioactive IL-16 levels secreted by CD4+T cells (193.5±43.1 ng/L) were significant lower than those secreted by CD8+T cells (377±100.2 ng/L) in Tuberculous pleural effusion. In contrast, bioactive IL-16 concentrations secreted by CD4+T cells (352.8±100.2 ng/L) were significant higher than those secreted by CD8+T cells (261.5±62.2 ng/L) in malignant PE.III. The mechanism involved in IL-16 increasment in pleural effusionThere is no difference of intracellular IL-16 protein levels but great difference of secreted active IL-16 levels between CD4+T cells and CD8+T cells in PE. We hypothesized that this critical difference might lie with Caspase-3 activation. It was reported active Caspase-3 was an important mechanism for pro-IL-16 processing and bioactive IL-16 releasing. FCM was used to detect the percentage of CD3+CD8+active Caspase-3+T cells, CD3+CD8-active Caspase-3+T cells and CD19+active Caspase-3+B cells in PE and PB from both TB patients and Malignant patients. Our data showed an obviously increase of the percentages of active Caspase-3 in CD3+CD8-T cells (4.4±1.1%) in comparison with CD3+CD8+T cells (2.7±0.6%) in PE from Tuberculous patients.IV. Active IL-16 released by T cells may participate in development of TB diseaseThe greater levels of IFN-gamma, IL-12p40 and IL-18 in tuberculous pleural effusion than in malignant pleural effusion demonstrated T cells in tuberculous pleural effusions are polarized to Thl, and Th2 may be dominant in malignant pleural effusion. Elizabeth has used T cells from CCR5null mice and determined CCR5 significantly increased IL-16 binding to CD4 and IL-16-induced migration. CCR5 was expressed predominantly in Thl cells, so IL-16 could preferentially chemoattract Thl cells. So IL-16 may participate in the induction and development of TB disease.Based on our data, one could hypothesize that CD8+T cells may represent a more rapidly release mechanism of IL-16 in tuberculous PE, and would contribute to recruitment of CD4+T cells by secretion of bioactive IL-16. Consequently, the CD4+T cells which migrating from other place into PE secrete more IL-16 and serve to function as a positive feedback mechanism for further cell recruitment and activation. It is the possible process for IL-16 involved in the development of TB disease.Conclusion1. Increased IL-16 released in tuberculous pleural effusion2. In comparion with other cells, T cells express higher levels of IL-16 protein, T cells are the main source of IL-16 in pleural effusion. The increasing of T cells amount is positively correlated with higher secreted IL-16 levels in TB pleural effusion.3. Caspase-3 may not be the unique enzyme for pro-IL-16 processing, some other proteins or enzymes have also involved in processing and secretion of IL-16.4. In different types of cells, there are different pathway for IL-16 secretion5. IL-16 may participate in development of TB disease, through preferentially chemoattracting Thl cells into pleural effusion...
Keywords/Search Tags:T cells, B cells, tuberculous PE/PB, malignant PE/PB, IL-16, Caspase-3
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