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

• Published in: Scandinavian journal of immunology Vol. 97; no. 4; pp. e13248 - n/a
• Main Authors: Bergantini, Laura, d'Alessandro, Miriana, Cavallaro, Dalila, Pordon, Elena, Cassai, Lucia, Gangi, Sara, Meloni, Federica, Montagnani, Francesca, Paladini, Piero, Refini, Rosa Metella, Luzzi, Luca, Fossi, Antonella, Bargagli, Elena, Bennett, David
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2023; Wiley-Blackwell
• Subjects: Antigens; CD137 antigen; CD4 antigen; CD40L protein; CD56 antigen; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell injury; checkpoint inhibitor; CTLA-4 protein; Cytomegalovirus; Cytomegalovirus - physiology; Cytomegalovirus Infections; Cytotoxicity; Flow cytometry; Humans; Immune checkpoint; Immunoglobulin G; immunology; Lung; Lung Diseases; lung transplant; Lung transplantation; Lung transplants; Lymphocytes T; Morbidity; Pp65 protein; Programmed Cell Death 1 Receptor; T-Lymphocytes - immunology; cytomegalovirus; lung transplant; immunology; checkpoint inhibitor
• ISSN: 0300-9475; 1365-3083; 1365-3083
• DOI: 10.1111/sji.13248

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.