Longitudinal Analysis of the Phenotype, Transcriptional Profile, and Anatomic Location of Memory CD8 T Cell Subsets after Acute Viral Infection.
J Virol
; 97(1): e0155622, 2023 01 31.
Article
em En
| MEDLINE
| ID: mdl-36541799
ABSTRACT
Increased demand for novel, highly effective vaccination strategies necessitates a better understanding of long-lived memory CD8 T cell differentiation. To achieve this understanding, we used the mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. We reexamined classical memory CD8 T cell subsets and performed in-depth, longitudinal analysis of their phenotype, transcriptional programming, and anatomic location within the spleen. All analyses were performed at multiple time points from 8 days to 1 year postinfection. Memory subsets are conventionally defined by their expression of KLRG1 and IL-7Rα, as follows KLRG1+IL-7Rα- terminal effectors (TEs) and KLRG1-IL-7Rα+ memory precursors (MPs). But we also characterized a third KLRG1+IL-7Rα+ subset which we refer to as KLRG1+ MPs. In these analyses, we defined a comprehensive memory phenotype that is associated with higher levels of CD28 expression. We also demonstrated that MPs, KLRG1+ MPs, and TEs have distinct localization programs within the spleen. We found that MPs became preferentially enriched in the white pulp as early as 1 to 2 weeks postinfection, and their predominance in the white pulp was maintained throughout the course of a year. On the other hand, KLRG1+ MPs and TEs localized to the red pulp just as early, and they consistently localized to the red pulp thereafter. These findings indicate that location may be crucial for memory formation and that white pulp-derived signals may contribute to long-term memory survival. Achieving robust memory responses following vaccination may require more deliberate consideration of which memory phenotypes are induced, as well as where they traffic, as these factors could impact their longevity. IMPORTANCE CD8 T cells play a critical role in viral immunity and it is important to understand how memory cells are formed and what processes lead to their long-term maintenance. Here, we use a mouse model of acute infection to perform an in-depth, longitudinal analysis of memory CD8 T cell differentiation, examining the phenotype and location of memory cells out to 1 year postinfection.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Coriomeningite Linfocítica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Virol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos