A human memory T-cell subset with stem cell-like properties

By L. Gattinoni, E. Lugli, Yun Ji, Z. Pós, C. Paulos, Maire F. Quigley, J. Almeida, E. Gostick, Zhiya Yu, C. Carpenito and 7 more. Nature Medicine, 2011

1,888 citations recorded by the source corpus.

Immunological memory is thought to depend on a stem cell–like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO−, CCR7+, CD45RA+, CD62L+, CD27+, CD28+ and IL-7Rα+ T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2Rβ, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell–like memory T cell population is of direct relevance to the design of vaccines and T cell therapies.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/0a1b8ee59d148c8f3e13b62538091d4a3adcafad

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Citations in the corpus

Single-cell RNA-seq: advances and future challenges (2014, positive): “…individual markers can be used simultaneously (46,47), which enables complex immuno-phenotyping that can identify novel subsets of cells even within previously well-characterized cell populations, for example, a T cell sub-population with stem-cell-like memory and high proliferative capacity (48).”
Background fluorescence and spreading error are major contributors of variability in high‐dimensional flow cytometry data visualization by t‐distributed stochastic neighboring embedding (2018, methodology): “Therefore, we selected highly puri-ﬁ ed CD8 + naive T (T N ) cells on the basis of a combination of six markers that are known to be associated with naivety (i.e., CD45RA + CCR7 + CD27 + CD95 − Tbet − CD73 + ; Figure 1c) (16,17) and plotted them on top of the tSNE map.”
Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets (2012, positive): “The low proportion of CD8 Tcm cells compared to CD4 Tcm cells was not predicted from analysis of peripheral blood (Gattinoni et al., 2011; Sallusto et al., 1999) and is most striking when comparing whole body subset delineation as accomplished here.”
Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo (2015, neutral): “T M are further divisible into central (T CM ) and effector memory (T EM ) subsets that differ in phenotype, transcriptional profile, and self-renewal capacity 17–19 .”