Virus-Specific Stem Cell Memory CD8+ T Cells May Indicate a Long-Term Protection against Evolving SARS-CoV-2
Open Access
- 28 March 2023
- journal article
- research article
- Published by MDPI AG in Diagnostics
- Vol. 13 (7), 1280
- https://doi.org/10.3390/diagnostics13071280
Abstract
Immune memory to SARS-CoV-2 is key for establishing herd immunity and limiting the spread of the virus. The duration and qualities of T-cell-mediated protection in the settings of constantly evolving pathogens remain an open question. We conducted a cross-sectional study of SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at several time points over 18 months (30–750 days) post mild/moderate infection with the aim to identify suitable methods and biomarkers for evaluation of long-term T-cell memory in peripheral blood. Included were 107 samples from 95 donors infected during the periods 03/2020–07/2021 and 09/2021–03/2022, coinciding with the prevalence of B.1.1.7 (alpha) and B.1.617.2 (delta) variants in Bulgaria. SARS-CoV-2-specific IFNγ+ T cells were measured in ELISpot in parallel with flow cytometry detection of AIM+ total and stem cell-like memory (TSCM) CD4+ and CD8+ T cells after in vitro stimulation with peptide pools corresponding to the original and delta variants. We show that, unlike IFNγ+ T cells, AIM+ virus-specific CD4+ and CD8+ TSCM are more adequate markers of T cell memory, even beyond 18 months post-infection. In the settings of circulating and evolving viruses, CD8+ TSCM is remarkably stable, back-differentiated into effectors, and delivers immediate protection, regardless of the initial priming strain.Funding Information
- Bulgarian National Science Fund (KP-06-DK1/9/29.03.2021)
- National Institute of Allergy and Infectious Diseases (No. 75N93021C00065)
This publication has 36 references indexed in Scilit:
- Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19Nature Immunology, 2020
- Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19Signal Transduction and Targeted Therapy, 2020
- Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndromeScience Immunology, 2020
- Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed IndividualsCell, 2020
- T memory stem cells in health and diseaseNature Medicine, 2017
- A human memory T cell subset with stem cell–like propertiesNature Medicine, 2011
- The Yellow Fever Virus Vaccine Induces a Broad and Polyfunctional Human Memory CD8+ T Cell ResponseThe Journal of Immunology, 2009
- Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsetsBlood, 2009
- CD4+ memory T cells: functional differentiation and homeostasisImmunological Reviews, 2006
- Antigen Burden Is a Major Determinant of Human Immunodeficiency Virus–Specific CD8+T Cell Maturation State: Potential Implications for Therapeutic ImmunizationThe Journal of Infectious Diseases, 2003