Revisiting CD8 T-cell ‘Memory Inflation’: New Insights with Implications for Cytomegaloviruses as Vaccine Vectors

Autor: Rafaela Holtappels, Kirsten Freitag, Angelique Renzaho, Sara Becker, Niels A.W. Lemmermann, Matthias J. Reddehase
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Vaccines, Vol 8, Iss 3, p 402 (2020)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines8030402
Popis: Murine models of cytomegalovirus (CMV) infection have revealed an exceptional kinetics of the immune response. After resolution of productive infection, transient contraction of the viral epitope-specific CD8 T-cell pool was found to be followed by a pool expansion specific for certain viral epitopes during non-productive ‘latent’ infection. This phenomenon, known as ‘memory inflation’ (MI), was found to be based on inflationary KLRG1+CD62L− effector-memory T cells (iTEM) that depend on repetitive restimulation. MI gained substantial interest for employing CMV as vaccine vector by replacing MI-driving CMV epitopes with foreign epitopes for generating high numbers of protective memory cells specific for unrelated pathogens. The concept of an MI-driving CMV vector is questioned by human studies disputing MI in humans. A bias towards MI in experimental models may have resulted from systemic infection. We have here studied local murine CMV infection as a route that is more closely matching routine human vaccine application. Notably, KLRG1−CD62L+ central memory T cells (TCM) and conventional KLRG1−CD62L− effector memory T cells (cTEM) were found to expand, associated with ‘avidity maturation’, whereas the pool size of iTEM steadily declined over time. The establishment of high avidity CD8 T-cell central memory encourages one to pursue the concept of CMV vector-based vaccines.
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