Modulation of human T‐cell functions by reactive nitrogen species

Kasic, Tihana; Colombo, Piergiuseppe; Soldani, Cristiana; Wang, Chiuhui Mary; Miranda, Elena; Roncalli, Massimo; Bronte, Vincenzo; Viola, Antonella

doi:10.1002/eji.201040868

Cited by 58 publications

(47 citation statements)

References 24 publications

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“…These include production of reactive oxygen and nitrogen species (ROS & RNS) that are generated by the inducible nitric oxide synthase (iNOS) and NADPH oxidase enzymes, and depletion of key nutrients required for normal function of T-cells, especially arginine by activation of arginase, and tryptophan and cysteine by sequestration in tumor-specific T-cells 1–6 . Additionally, activation of T-cells can be impaired by nitration of their antigen or chemokine receptors 7 , or suppressed by induction of T regulatory cells via TGF-β produced by MDSC. 8 …”

Section: Introductionmentioning

confidence: 99%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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BACKGROUND Subsets of myeloid-derived regulatory cells (MDRC), phenotypically similar to myeloid-derived suppressor cells found in cancer, have recently been appreciated as critical regulators of airway inflammation in mouse models of asthma. OBJECTIVE We test the hypothesis that subsets of airway MDRC contribute differentially to the inflammatory milieu in human asthma and chronic obstructive pulmonary disease (COPD). METHODS We used BAL to identify and characterize human airway MDRC from 10 normal, 9 mild asthmatic and 8 COPD subjects, none treated with inhaled or systemic corticosteroids. We defined subsets of airway MDRC by flow cytometry, the molecular mediators they produce and their abilities to regulate proliferation of polyclonally activated autologous T-lymphocytes. RESULTS We found substantial differences in the functional potential of MDRC subsets in normal, asthmatic and COPD subjects, with these differences regulated by the nitrosative and oxidative free radicals and cytokines they produced. Nitric oxide-producing MDRC suppressed and superoxide-producing MDRC enhanced proliferation of polyclonally activated autologous CD4 T-cells. HLA-DR+CD11+CD11c+CD163− superoxide-producing MDRC, which stimulated proliferation of autologous T-cells, comprised a high fraction of MDRC in airways of subjects with mild asthma or COPD, but not normals. CD11b+CD14+CD16−HLA-DR− nitric oxide-producing MDRC, which suppressed T-cell proliferation, were present in high numbers in airways of subjects with mild asthma, but not subjects with COPD or normals. CONCLUSION Subsets of airway MDRC conclusively discriminate mild asthmatics, subjects with COPD and normal subjects from each other. The distinctive activities of these MDRC in asthma and COPD may provide novel targets for new therapeutics in these common disorders.

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Section: Introductionmentioning

confidence: 99%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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“…We then investigated whether the presence of reactive nitrogen plays a role in the differential distribution of CD8 + T cells within fibrous septa and tumor lobules (31). Staining with the nitrotyrosine-specific mAb showed that the T-lymphocyte distribution mirrored the nitrotyrosine staining (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma

Sabbatino

Villani

Yearley

et al. 2016

Clinical Cancer Research

182

165

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Purpose More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Experimental Design Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Results Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8+ T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. Conclusions ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.

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“…The involvement of iNOS in the generation of Tlymphoctye-derived NO and its role in inhibiting T lymphocyte proliferation have been documented (108,135). Vig et al have shown that iNOS production in activated T cells regulates T-cell death and immune memory (295).…”

Section: Interestingly Studies Indicate a Role Of Mnsod Inactivationmentioning

confidence: 99%

Redox Regulation of T-Cell Function: From Molecular Mechanisms to Significance in Human Health and Disease

Kesarwani

Murali

Al-Khami

et al. 2013

Antioxidants & Redox Signaling

195

165

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Modulation of human T‐cell functions by reactive nitrogen species

Cited by 58 publications

References 24 publications

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma

Redox Regulation of T-Cell Function: From Molecular Mechanisms to Significance in Human Health and Disease

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