The Prothrombin Gene

MacGillivray, Ross T. A.; Irwin, David M.

doi:10.1159/000215295

Cited by 2 publications

(1 citation statement)

References 42 publications

(68 reference statements)

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“…The adoptive transfer of virus‐specific cytotoxic T lymphocytes (CTLs) directed against cytomegalovirus (CMV) , Epstein–Barr virus (EBV) and adenovirus (ADV) can safely and effectively reduce or prevent the clinical manifestations of these viruses in immunosuppressed patients after haematopoietic stem cell transplantation and solid organ transplantation. Prophylactic anti‐viral drug treatments are effective at preventing invasive viral infections post‐transplant, but are typically administered for a limited time due to cumulative drug toxicity and cost . However, hosts with impaired T cell immunity remain susceptible to subsequent infections.…”

Section: Introductionmentioning

confidence: 99%

Modulation of heme oxygenase-1 by metalloporphyrins increases anti-viral T cell responses

Bunse

Fortmeier

Tischer

et al. 2015

Clinical and Experimental Immunology

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Heme oxygenase (HO)-1, the inducible isoform of HO, has immunomodulatory functions and is considered a target for therapeutic interventions. In the present study, we investigated whether modulation of HO-1 might have regulatory effects on in-vitro T cell activation. The study examined whether: (i) HO-1 induction by cobalt-protoporphyrin (CoPP) or inhibition by tin-mesoporphyrin (SnMP) can affect expansion and function of virus-specific T cells, (ii) HO-1 modulation might have a functional effect on other cell populations mediating effects on proliferating T cells [e.g. dendritic cells (DCs), regulatory T cells (T(regs)) and natural killer cells] and (iii) HO-1-modulated anti-viral T cells might be suitable for adoptive immunotherapy. Inhibition of HO-1 via SnMP in cytomegalovirus (CMV)pp65-peptide-pulsed peripheral blood mononuclear cells (PBMCs) led to increased anti-viral T cell activation and the generation of a higher proportion of effector memory T cells (CD45RA(-) CD62L(-)) with increased capability to secrete interferon (IFN)-γ and granzyme B. T(reg) depletion and SnMP exposure increased the number of anti-viral T cells 15-fold. To test the possibility that HO-1 modulation might be clinically applicable in conformity with good manufacturing practice (GMP), SnMP was tested in isolated anti-viral T cells using the cytokine secretion assay. Compared to control, SnMP treatment resulted in higher cell counts and purity without negative impact on quality and effector function [CD107a, IFN-γ and tumour necrosis factor (TNF)-α levels were stable]. These results suggest an important role of HO-1 in the modulation of adaptive immune responses. HO-1 inhibition resulted in markedly more effective generation of functionally active T cells suitable for adoptive T cell therapy.

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Section: Introductionmentioning

confidence: 99%