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ISBN 9783843920643

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978-3-8439-2064-3, Reihe Medizin

Patricia Gräf
Serial transfer of single cell-derived immunocompetence reveals stemness of CD8+ central memory T cells

170 Seiten, Dissertation Technische Universität München (2014), Hardcover, A5

Zusammenfassung / Abstract

Maintenance of immunological memory has been proposed to rely on stem-cell-like lymphocytes. However, data supporting this hypothesis are focused on the developmental potential of lymphocyte populations and are thus, insufficient to establish the functional hallmarks of stemness. Here, we investigated self-renewal capacity and multipotency of individual memory lymphocytes by in vivo fate mapping of CD8+ T cells and their descendants across three generations of serial single cell adoptive transfer and infection-driven re-expansion. We found that immune responses derived from single naïve T (TN) cells, single primary and single secondary central memory T (TCM) cells reached similar size and phenotypic diversity, were subjected to comparable stochastic variation and could ultimately reconstitute immunocompetence against an otherwise lethal infection with the bacterial pathogen Listeria monocytogenes. These observations establish that adult tissue stem cells reside within the CD62L+ TCM compartment and highlight the promising therapeutic potential of this immune cell subset.