T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.

Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans / G. Galletti, G. De Simone, E.M.C. Mazza, S. Puccio, C. Mezzanotte, T.M. Bi, A.N. Davydov, M. Metsger, E. Scamardella, G. Alvisi, F. De Paoli, V. Zanon, A. Scarpa, B. Camisa, F.S. Colombo, A. Anselmo, C. Peano, S. Polletti, D. Mavilio, L. Gattinoni, S.K. Boi, B.A. Youngblood, R.E. Jones, D.M. Baird, E. Gostick, S. Llewellyn-Lacey, K. Ladell, D.A. Price, D.M. Chudakov, E.W. Newell, M. Casucci, E. Lugli. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - 21:12(2020 Dec), pp. 1552-1562. [10.1038/s41590-020-0791-5]

Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans

E.M.C. Mazza
Membro del Collaboration Group
;
F. De Paoli
Membro del Collaboration Group
;
V. Zanon
Membro del Collaboration Group
;
F.S. Colombo
Membro del Collaboration Group
;
S. Polletti;D. Mavilio;L. Gattinoni
Membro del Collaboration Group
;
M. Casucci
Penultimo
;
2020

Abstract

T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/04 - Patologia Generale
Settore MED/06 - Oncologia Medica
ott-2020
Article (author)
File in questo prodotto:
File Dimensione Formato  
D:Galletti at al. Nature Immunology.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 11.16 MB
Formato Adobe PDF
11.16 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/777866
Citazioni
  • ???jsp.display-item.citation.pmc??? 52
  • Scopus 82
  • ???jsp.display-item.citation.isi??? 80
social impact