Investigating the heterogeneity of T Stem Cell Memory cell (Tscm) and their role in maintenance of long-term immunity following vaccination in humans
File(s)
Author(s)
Kaur, Charandeep
Type
Thesis
Abstract
Memory T cells, with their critical role in immune responses, have become a central focus of research in the field of immunology. Among these memory T cells, Tscm (memory stem cells) has gathered significant attention due to their stem-like characteristics, including self-renewal and multipotency, suggesting a role in maintaining long-term immunity. Building upon prior research conducted by our laboratory, we have uncovered the existence of kinetic heterogeneity within the Tscm compartment, leading to the identification of two distinct subpopulations based on CD95 expression: CD95hi and CD95int.
This thesis investigates the characteristics of these Tscm subpopulations and their role in the maintenance of long-term immunity. Our study begins by validating kinetic heterogeneity within the Tscm compartment, involving the examination of proliferation markers, cell division history, age-related trends, and their tissue distributions. Additionally, by investigating the dynamics of HIV specific-Tscm subsets following HIV vaccination in healthy volunteers we concluded that CD95hi and CD95int have distinct identities and both subsets play essential roles in memory maintenance.
CD95int cells exhibit a quiescent profile characterized by low proliferation rates, relative stability with aging, prevalence in human lymph nodes, and the persistent low expression of activation and co-stimulatory molecules. In contrast, the CD95hi subset presents an activated phenotype with higher proliferation rates, increased activation molecule expression and accumulates with age. In HIV trial vaccination studies, both subsets display unique dynamics post-vaccination, with CD95int being less prominent while CD95hi demonstrates a high frequency at all the timepoints post-boost and exhibits a significant correlation with the rate of decay of HIV specific CD8+T memory.
In conclusion, our findings highlight that CD95 expression can distinguish the two proposed subpopulations within the Tscm compartment. Despite different dynamics, both subsets contribute significantly to memory maintenance.
This thesis investigates the characteristics of these Tscm subpopulations and their role in the maintenance of long-term immunity. Our study begins by validating kinetic heterogeneity within the Tscm compartment, involving the examination of proliferation markers, cell division history, age-related trends, and their tissue distributions. Additionally, by investigating the dynamics of HIV specific-Tscm subsets following HIV vaccination in healthy volunteers we concluded that CD95hi and CD95int have distinct identities and both subsets play essential roles in memory maintenance.
CD95int cells exhibit a quiescent profile characterized by low proliferation rates, relative stability with aging, prevalence in human lymph nodes, and the persistent low expression of activation and co-stimulatory molecules. In contrast, the CD95hi subset presents an activated phenotype with higher proliferation rates, increased activation molecule expression and accumulates with age. In HIV trial vaccination studies, both subsets display unique dynamics post-vaccination, with CD95int being less prominent while CD95hi demonstrates a high frequency at all the timepoints post-boost and exhibits a significant correlation with the rate of decay of HIV specific CD8+T memory.
In conclusion, our findings highlight that CD95 expression can distinguish the two proposed subpopulations within the Tscm compartment. Despite different dynamics, both subsets contribute significantly to memory maintenance.
Version
Open Access
Date Issued
2023-10-20
Date Awarded
2024-03-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Asquith, Becca
Pollock, Katrina
Kibirige, Catherine N
Sponsor
European Commission
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)