Articles: regulatory-t-lymphocytes.
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Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of Th cells with opposing actions which participate in the process of resolving acute lung injury (ALI). Glutamine (Gln) is a nutrient commonly used in nutrition regimens due to its immunomodulatory effects. This study investigated whether alanyl-glutamine (Ala-Gln) administration modulated polarization of Th subsets in a model of lipopolysaccharide (LPS)-induced ALI during the resolution period. ⋯ Expressions of proinflammatory-related and fibrosis-related genes in lung tissues decreased in the Gln group. Histopathological findings also showed that interstitial inflammation was less severe in the Gln group. These results suggest that Ala-Gln administration after the onset of ALI can help resolve lung inflammation and injury by modulating the polarization of Tregs and Th17 cells.
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T regulatory cells (Tregs) have been associated with prolonged allograft survival and tolerance across a wide variety of species and organ types. We used our nonhuman primate model of facial vascularized composite allotransplantation (VCA) to study the association of Tregs with graft outcomes. ⋯ These findings in a clinically relevant model suggest that Tregs may have limited prognostic value with standard immunosuppressive protocols used in VCA. Further studies are necessary to determine the specific role of Tregs in VCA and any role of Treg monitoring in clinical practice.
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Transcription factor cAMP response element modulator (CREM)α contributes to various cellular and molecular abnormalities in T cells, including increased IL-17 and decreased IL-2 expression. For development of acute lung injury (ALI), the invasion and regulation of immune cells are highly important, but the role of T cells remains unclear. In this study, we show that CREMα is upregulated in LPS-induced ALI. ⋯ Finally, an adoptive transfer of CREM(-/-) CD4(+) T cells, but not of wild-type T cells into RAG-1(-/-) mice results in ameliorated disease levels. Thus, levels of CREM in T cells determine the outcome of ALI, and CREMα transgenic animals represent a model in which proinflammatory T cells aggravate ALI in different phases of the disease. Given the fact that patients with autoimmune diseases like systemic lupus erythematosus show higher levels of CREMα and an increased susceptibility toward infectious complications, our finding is of potential clinical significance and may enable new therapeutic strategies.
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Vascularized composite allografts (VCAs) are unique among transplanted organs in that they are composed of multiple tissues with disparate antigenic and immunologic properties. As the predominant indications for VCAs are non-life-threatening conditions, there is an immediate need to develop tolerance induction strategies and to elucidate the mechanisms of VCA rejection and tolerance using VCA-specific animal models. In this study, we explore the effects of in vitro induced donor antigen-specific CD4(-) CD8(-) double negative (DN) Treg-based therapy, in a fully MHC mismatched mouse VCA such as a vascularized osteomyocutaneous as compared to a non-VCA such as a full thickness skin (FTS) transplantation model to elucidate the unique features of VCA rejection and tolerance. ⋯ Macrochimerism was detected in VCA but not FTS allograft recipients up to >60 days after transplantation. Moreover, a significant increase of CD4(+) Foxp3(+) Tregs was found in the peripheral blood of tolerant VCA recipients. These data suggest that VCA are permissive to tolerance induced by DN Treg-based induction therapy.
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Clin. Exp. Immunol. · Aug 2013
Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of the symptoms, therapeutic strategies have been ineffective. High mobility group box 1 (HMGB1), which was identified originally as a DNA binding protein, has been proposed as a mediator of acute lung injury. ⋯ HMGB1 was expressed in the infiltrating neutrophils and macrophages in lungs. T(reg) cells were reduced significantly in the lungs of ARDS mice compared to those in mice treated with LPS alone. rTM administration prolonged the survival time and ameliorated the development of ARDS, which was associated with increased T(reg) cells and synthesis of interleukin (IL)-10 and transforming growth factor (TGF)-β in the lungs. These results suggest that HMGB1 is involved in the development of severe ARDS and rTM shows therapeutic effects through promoting the accumulation of T(reg) cells at the inflammatory sites.