Title: Immune checkpoint analysis of T‐cell responses to pp65 and IE‐1 antigens in end‐stage lung diseases

Journal Article · · Scandinavian Journal of Immunology
DOI: https://doi.org/10.1111/sji.13248 · OSTI ID:1907903
ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [4];  [1];  [4];  [1]; ORCiD logo [1];  [1]
  1. Respiratory Disease Unit, Department of Medical Sciences University Hospital of Siena (Azienda Ospedaliera Universitaria Senese, AOUS) Siena Italy
  2. University of Pavia pavia Italy, Department of Haematological, Pneumological and Cardiovascular Sciences Fondazione IRCCS Policlinico San Matteo pavia Italy
  3. Department of Medical Biotechnologies University of Siena Siena Italy, Department of Medical Sciences Infectious and Tropical Diseases Unit, University Hospital of Siena Siena Italy
  4. Thoracic Surgery Unit, Cardio‐Thoracic and Vascular Department University Hospital of Siena (Azienda Ospedaliera Universitaria Senese, AOUS) Siena Italy
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Abstract Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD‐1, CTLA‐4, LAG‐3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end‐stage patients awaiting lung transplant. Eighteen pre‐LTX positive for anti‐CMV IgG titres and 18 healthy subjects were enrolled. IC and activation markers have been evaluated through flow cytometric analysis in HC and pre‐LTX patients. Reactive (QF+) and unreactive (QF−) patients were stratified according to QuantiFERON‐CMV assays. ICs' and activation markers' expression were determined before and after in vitro stimulation with pp‐65 and IE‐1 antigens. Lower expression of PD‐1 was observed in CD4 and CD8 cells of pre‐LTX patients than controls, whereas CTLA4 appeared upregulated in CD56 and CD8 cells. TIGIT is increased on the surface of CD4, CD8 and NK cells after peptide stimulation in QF‐negative patients and PD‐1 is only downregulated after stimulation in the QF‐positive patients. This study provides new evidence of immune dysregulation in patients with end‐stage lung disorders, particularly in relation to immune checkpoint cell biology. The change in QF+ mostly happens on cytotoxic cells NK and CD8, while the changes in QF− were observed in adaptive immune cells, including CD4 and CD8.

Sponsoring Organization:
USDOE
OSTI ID:
1907903
Journal Information:
Scandinavian Journal of Immunology, Journal Name: Scandinavian Journal of Immunology Journal Issue: 4 Vol. 97; ISSN 0300-9475
Publisher:
Wiley-BlackwellCopyright Statement
Country of Publication:
Norway
Language:
English

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