CD8+ T cells specific to apoptosis-associated epitopes are expanded in patients with chronic HBV infection and fibrosis
| Autor: | Ilenia Cammarata, Silvia Piconese, Vincenzo Barnaba, Giuseppina Brancaccio, Giovanni Battista Gaeta, Carmela Martire, Ilenia Pacella |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
treg
Hepatology medicine.diagnostic_test T cell autoimmunity fibrosis chronic HBV infection Biology medicine.disease_cause Epitope Flow cytometry Autoimmunity 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Immunopathology Immunology medicine Cytotoxic T cell 030211 gastroenterology & hepatology Treg CD8 |
| Popis: | Background & aims During chronic viral infections, the apoptosis of activated T cell elicits a CD8+ T cell response directed to those cryptic epitopes that emerge from caspase-cleaved structural proteins. Such response directed to apoptosis-associated epitopes (AEs) contributes to the amplification of immunopathology. Methods Here, we have analysed through flow cytometry AE-specific CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, naive-to-treatment or undergoing nucleos(t)ide-analogue (NUC) therapy. Results We found that AE-specific CD8+ T cell frequencies were significantly increased only in those NUC-treated patients who also presented advanced hepatic fibrosis. Regulatory T cells were also expanded in those patients, and AE-specific, but not HBV-specific, CD8+ T cell frequency positively correlated with Treg percentages. Through multiparameter flow cytometry, multidimensionality reduction and unsupervised clustering analysis, we could identify novel subpopulations among effector memory (em) and emCD45RA+ T cell (Tem and Temra) subsets. CD8+ T cells with distinct specificities differentially populated the subpopulation map: while HBV-specific were mostly contained in the Tem subset, AE-specific CD8+ T cells encompassed naive, as well as T central memory, Tem and Temra cells. Conclusion All together, these findings indicate a link between AE-specific CD8+ T cells and advanced liver fibrosis in patients with chronic HBV infection, and suggest that virus-specific and AE-specific CD8+ T cells exhibit distinct differentiation states and contribute in distinct ways to immunopathology. |
| Databáze: | OpenAIRE |
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