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

PLoS Pathogens

Ramakrishna Sompallae¹  Vladimir P. Badovinac¹  Marie T. Kim²  John T. Harty³  Matthew D. Martin³  Qiang Shan³  Hai-Hui Xue⁴ 

[1] Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America;Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America;Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America;Iowa Institute of Human Genetics Bioinformatics Division, University of Iowa, Iowa City, Iowa, United States of America

关键词: Cytotoxic T cells;    Memory T cells;    T cells;    Cell staining;    Gene expression;    Spleen;    Cytokines;    Vaccination;    immunization;   

DOI  :  10.1371/journal.ppat.1005219

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY