Articles: regulatory-t-lymphocytes.
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Acute lung injury (ALI) is characterized by rapid alveolar injury, inflammation, cytokine induction, and neutrophil accumulation. Although early events in the pathogenesis of ALI have been defined, the mechanisms underlying resolution are unknown. As a model of ALI, we administered intratracheal (i.t.) LPS to mice and observed peak lung injury 4 days after the challenge, with resolution by day 10. ⋯ Mechanistically, Treg-mediated resolution of lung injury was abrogated by TGF-beta inhibition. Moreover, BAL of patients with ALI revealed dynamic changes in CD3+CD4+CD25hiCD127loFoxp3+ cells. These results indicate that Tregs modify innate immune responses during resolution of lung injury and suggest potential targets for treating ALI, for which there are no specific therapies currently available.
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J. Allergy Clin. Immunol. · Sep 2009
Comparative StudyDistinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese.
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. ⋯ Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced T(H)1/T(H)2/T(H)17 responses. CRSsNP is confirmed to be a predominant T(H)1 milieu, whereas T(H)2 skewed inflammation with predominant T(H)17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.
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Expert Rev Clin Immunol · Sep 2009
Prostate autoimmunity: from experimental models to clinical counterparts.
Different murine models of autoimmune prostatitis have been developed and characterized, proving the autoimmune origin of this pathology. Autoimmune prostatitis models have also provided a wealth of information on the mechanisms involved in disease development, shedding light on inciting autoantigens, regulatory and pathogenic T cells, and mediators of prostatic autoimmunity. ⋯ In this review, we will discuss evidence for the autoimmune origin of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the chronic inflammatory nature of benign prostatic hyperplasia (BPH). The autoimmune pathogenesis of CP/CPPS and the chronic inflammation characteristic of BPH will be reviewed within the context of the recent demonstration that human prostate stromal cells from BPH tissue can act as antigen-presenting cells and are not only able to activate CD4(+) T lymphocytes, but can also produce IL-12 and IL-23, which are key cytokines for the induction of pathogenic Th1 and Th17 cells.
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Acta Biochim. Biophys. Sin. (Shanghai) · Sep 2009
A glucocorticoid amplifies IL-2-induced selective expansion of CD4(+)CD25(+)FOXP3(+) regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation.
Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously administered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4(+)CD25(+)FOXP3(+) T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/ Teff ) ratio to prevent graft-versus-host disease (GVHD). ⋯ The ratio of Treg/Teff also increased remarkably (0.43+/-0.15 vs. 0.14+/-0.01, P=0.01). This study demonstrated that co-stimulation with Dex and IL-2 selectively expanded functional CD4(+)CD25(+)FOXP3(+) T cells in vivo, and that grafts from donors pre-treated with Dex and IL-2 led to longer survival time and greater suppression of GVHD after allogeneic transplantation. Thus, GVHD can be suppressed by the specific expansion of regulatory T cells with Dex and IL-2 in graft donors.
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Regulatory T cells (Tregs) expressing TCRalphabeta play a critical role in the maintenance of the immune system homeostasis. Tregs express the cell surface markers CD4 and CD25 as well as the transcription factor Foxp3. Foxp3(+)CD4(+)CD25(+)TCRalphabeta(+) Tregs can be generated from mouse and human CD4(+)CD25(-) T cells in vitro via TGF-beta induction. ⋯ Furthermore, the TGF-beta induced gammadelta T cells mediated a potent immunosuppressive effect on anti-CD3 stimulated T cell activation and proliferation. In contrast, although a small fraction of human peripheral blood and tumor infiltrating gammadelta T cells expressed Foxp3, similar culture condition with anti-TCRgammadelta plus TGF-beta failed to generate functional human Foxp3(+) gammadelta T cells. In conclusion, our results suggest that mouse splenic Foxp3(+) gammadelta T cells with suppressive function can be induced by TCR and TGF-beta costimulation, whereas functional human Foxp3(+) gammadelta T cells in peripheral blood could not be generated under the same condition.