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Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection
Journal article   Open access   Peer reviewed

Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection

Matthew D Martin, Marie T Kim, Qiang Shan, Ramakrishna Sompallae, Hai-Hui Xue, John T Harty and Vladimir P Badovinac
PLoS pathogens, Vol.11(10), pp.e1005219-e1005219
10/2015
DOI: 10.1371/journal.ppat.1005219
PMCID: PMC4618693
PMID: 26485703
url
https://doi.org/10.1371/journal.ppat.1005219View
Published (Version of record) Open Access

Abstract

Memory CD8 T cells confer increased protection to immune hosts upon secondary viral, bacterial, and parasitic infections. The level of protection provided depends on the numbers, quality (functional ability), and location of memory CD8 T cells present at the time of infection. While primary memory CD8 T cells can be maintained for the life of the host, the full extent of phenotypic and functional changes that occur over time after initial antigen encounter remains poorly characterized. Here we show that critical properties of circulating primary memory CD8 T cells, including location, phenotype, cytokine production, maintenance, secondary proliferation, secondary memory generation potential, and mitochondrial function change with time after infection. Interestingly, phenotypic and functional alterations in the memory population are not due solely to shifts in the ratio of effector (CD62Llo) and central memory (CD62Lhi) cells, but also occur within defined CD62Lhi memory CD8 T cell subsets. CD62Lhi memory cells retain the ability to efficiently produce cytokines with time after infection. However, while it is was not formally tested whether changes in CD62Lhi memory CD8 T cells over time occur in a cell intrinsic manner or are due to selective death and/or survival, the gene expression profiles of CD62Lhi memory CD8 T cells change, phenotypic heterogeneity decreases, and mitochondrial function and proliferative capacity in either a lymphopenic environment or in response to antigen re-encounter increase with time. Importantly, and in accordance with their enhanced proliferative and metabolic capabilities, protection provided against chronic LCMV clone-13 infection increases over time for both circulating memory CD8 T cell populations and for CD62Lhi memory cells. Taken together, the data in this study reveal that memory CD8 T cells continue to change with time after infection and suggest that the outcome of vaccination strategies designed to elicit protective memory CD8 T cells using single or prime-boost immunizations depends upon the timing between antigen encounters.
 Lymphocytic choriomeningitis virus - immunology T-Lymphocyte Subsets - immunology Oligonucleotide Array Sequence Analysis Mice, Inbred C57BL Molecular Sequence Data Immunophenotyping Adoptive Transfer Phenotype Animals Polymerase Chain Reaction Mice CD8-Positive T-Lymphocytes - immunology Arenaviridae Infections - immunology Immunologic Memory - immunology Disease Models, Animal

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