AUTHOR=Neitzke-Montinelli Vanessa , Calôba Carolina , Melo Guilherme , Frade Bianca B. , Caramez Enzo , Mazzoccoli Luciano , Gonçalves André N. A. , Nakaya Helder I. , Pereira Renata M. , Werneck Miriam B. F. , Viola João P. B. 

TITLE=Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.840203

DOI=10.3389/fimmu.2022.840203

ISSN=1664-3224

ABSTRACT=<p>Long-term immunological protection relies on the differentiation and maintenance of memory lymphocytes. Since the knowledge of memory generation has been centered on <italic>in vivo</italic> models of infection, there are obstacles to deep molecular analysis of differentiating subsets. Here we defined a novel <italic>in vitro</italic> CD8 T cell activation and culture regimen using low TCR engagement and cytokines to generate differentiated cells consistent with central memory-like cells, as shown by surface phenotype, gene expression profile and lack of cytotoxic function after challenge. Our results showed an effector signature expressed by <italic>in vitro</italic> memory precursors and their plasticity under specific conditions. Moreover, memory CD8 T cells conferred long-term protection against bacterial infection and slowed <italic>in vivo</italic> tumor growth more efficiently than effector cells. This model may allow further understanding of CD8 T cell memory molecular differentiation subsets and be suited for generating cells to be used for immunotherapy.</p>