Articles: regulatory-t-lymphocytes.
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We demonstrate herein that combination treatment with regulatory T cells (Tregs) and vascularized bone marrow transplantation (VBMT) can achieve stable mixed chimerism and long-term transplantation tolerance to vascularized composite allografts (VCA) without requiring cytoreductive recipient conditioning in rats. An appreciable number of Tregs of recipient origin was shown at the interface between recipient and transplanted VCA tissues, implicating a significant role for Tregs in protecting VCA from rejection. This cytoreduction-free protocol using co-treatment with Tregs and VBMT warrants further investigation toward potential clinical application for VCA transplantation.
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Int. Immunopharmacol. · Dec 2012
Imbalance of Th17/Treg cells in mice with chronic cigarette smoke exposure.
Recent studies have revealed that autoimmune responses mediated by CD4(+) T cells may contribute to the development of chronic obstructive pulmonary disease (COPD). Meanwhile, imbalance of Th17/Treg has been reported to play a key role in the pathogenesis of autoimmune diseases. However, information on Th17/Treg balance in COPD is relatively limited. ⋯ Our study thus reveals that the Th17/Treg imbalance exists in mice with chronic CS exposure, suggesting its potential role in the breakdown of immune self-tolerance in COPD. Further research on regulation of Th17/Treg balance may provide insights into the development of new therapeutic targets for this disease.
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Am. J. Respir. Crit. Care Med. · Nov 2012
BLT1-dependent alveolar recruitment of CD4(+)CD25(+) Foxp3(+) regulatory T cells is important for resolution of acute lung injury.
Recent study has demonstrated that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) present in bronchoalveolar lavage fluid (BALF) contribute to the resolution of an experimental acute lung injury (ALI). However, the molecular mechanism underlying the alveolar recruitment of Treg remains unclear. ⋯ Our findings reveal a novel antiinflammatory role of BLT1 in the resolution of ALI by mediating the alveolar recruitment of Tregs, and indicate that therapies aimed at interrupting the LTB4-BLT1 pathway after ALI onset could be harmful to the resolution of ALI.
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Studies have shown that an enhanced CD8+ T cell response and better tumor protection can be achieved by heterologous prime-boost vaccination in mice. Such heterologous vaccination can be more immunogenic than the homologous setting. We previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell (Treg)-directed suppression. ⋯ This tumor protection effect from heterologous prime-boost remained in the therapeutic model. When examining the Treg effect during the prime-boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. Our studies offer the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced antitumor effect in conjunction with DNA in a heterologous prime-boost protocol, and suggest that early Treg inhibition is crucial to a successful immunization against cancer.
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Journal of immunotherapy · Nov 2012
Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-α or TLR-9 agonist and GM-CSF with peptide vaccination.
Changes in the biomarkers of host suppressor immune response were evaluated in patients with melanoma enrolled in 2 trials. Two similar cohorts of patients participating in the 2 studies were evaluated. The first (IFN/treme) tested interferon (IFN)-α2b and tremelimumab in metastatic melanoma and reported a response rate of 24%, 6.4 months median progression-free survival, and 21 months median overall survival. ⋯ There were no significant changes in T-reg or MDSC, except for a trend towards decreased (HLA-DR(+) low/CD14(+)) MDSC at day 50 (P = 0.07). Therefore, IFN/treme significantly downregulated MDSC suggesting a role on the significant clinical activity observed in this trial. T-reg findings suggest that IFN/treme induced clinically significant antitumor responses by inhibiting CTLA4 suppressive effects on T effectors, and less so by affecting T-reg.