CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential
Open accessAbstract
In mice, the ability of naive T (TN) cells to mount an effector response correlates with TCR sensitivity for self-derived Ags, which can be quantified indirectly by measuring surface expression levels of CD5. Equivalent findings have not been reported previously in humans. We identified two discrete subsets of human CD8+ TN cells, defined by the absence or presence of the chemokine receptor CXCR3. The more abundant CXCR3+ TN cell subset displayed an effector-like transcriptional profile and expressed TCRs with physicochemical characteristics indicative of enhanced interactions with peptide–HLA class I Ags. Moreover, CXCR3+ TN cells frequently produced IL-2 and TNF in response to nonspecific activation directly ex vivo and differentiated readily into Ag-specific effector cells in vitro. Comparative analyses further revealed that human CXCR3+ TN cells were transcriptionally equivalent to murine CXCR3+ TN cells, which expressed high levels of CD5. These findings provide support for the notion that effector differentiation is shaped by heterogeneity in the preimmune repertoire of human CD8+ T cells.
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The gating strategy shown in this section is applicable for analysis of conventional αβ CD8+ T cells in any kind of physiological or clinical setting.
“The gating strategy shown in this section is applicable for analysis of conventional αβ CD8+ T cells in any kind of physiological or clinical setting [207, 208, 222].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [207]
The Methods (Flow cytometry and cell sorting; page unavailable) describe a gating strategy, and Figure 1A in the Results shows it for naive human CD8+ T-cell subsets. The paper examines samples from healthy individuals and patients with head and neck cancer, but it does not establish that the citing document’s strategy applies to conventional αβ CD8+ T cells in any physiological or clinical setting. (LLM, conf=0.86)
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References 79 · Cited by 49
- Authors
- De Simone, G., Mazza, E. M. C., Cassotta, A., Davydov, A. N., Kuka, M., Zanon, V., De Paoli, F., Scamardella, E., Metsger, M., Roberto, A., Pilipow, K., Colombo, F. S., Tenedini, E., Tagliafico, E., Gattinoni, L., Mavilio, D., Peano, C., Price, D. A., Singh, S. P., Farber, J. M., Serra, V., Cucca, F., Ferrari, F., Orrù, V., Fiorillo, E., Iannacone, M., Chudakov, D. M., Sallusto, F., & Lugli, E.
- Affiliations
- Laboratory of Translational Immunology, Humanitas Clinical and Research Center , 20089 Rozzano, Milan ,
- Humanitas University (IT)
- ETH Zurich (CH)
- Central European Institute of Technology (CZ)
- Vita-Salute San Raffaele University (IT)
- University of Modena and Reggio Emilia (IT)
- University Hospital Regensburg (DE)
- Cardiff University (GB)
- National Institutes of Health (US)
- Institute of Genetic and Biomedical Research (IT)
- IFOM (IT)
- Corresponding author
- Zanon, Veronica
- Scamardella, Eloise
- Roberto, Alessandra
- Pilipow, Karolina
- Gattinoni, Luca
- Lugli, Enrico
- ORCID
- Mazza, Emilia M C
- Cassotta, Antonino
- Davydov, Alexey N
- Kuka, Mirela
- Zanon, Veronica
- Metsger, Maria
- Roberto, Alessandra
- Pilipow, Karolina
- Colombo, Federico S
- Tenedini, Elena
- Tagliafico, Enrico
- Gattinoni, Luca
- Mavilio, Domenico
- Peano, Clelia
- Price, David A
- Singh, Satya P
- Farber, Joshua M
- Serra, Valentina
- Cucca, Francesco
- Ferrari, Francesco
- Orrù, Valeria
- Fiorillo, Edoardo
- Iannacone, Matteo
- Chudakov, Dmitriy M
- Sallusto, Federica
- Lugli, Enrico
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12
- Volume
- 203
- Issue
- 12
- Pages
- 3179-3189
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC6900484
- OpenAlex
- W2983661566
- Cited by
- 49
- References
- 79
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 14 · 2020: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- CNR ExploRA (submittedVersion, other-oa)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Funders
- National Science Foundation
- Giovanni Armenise-Harvard Foundation
- Emory University
- University of Minnesota
- Institute for Research in Biomedicine
- Wellcome Trust (100326, 100326/Z/12/Z)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (149475, 100326)
- Ministero della Salute (02347324, 82/2015, GR‐2011‐02347925)
- Associazione Italiana per la Ricerca sul Cancro (19891)
- Fondazione Italiana per la Ricerca sul Cancro
- Ministry of Science and Higher Education of the Russian Federation
- Helmut Horten Stiftung
- Humanitas Research Hospital
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- H2020 European Research Council (640511, 725038)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- CXCR3, naive CD8+ T cells, effector differentiation, T cell receptor repertoire, chemokine receptors, CD5, interleukin-2, TNF-α, T cell heterogeneity, gene expression profiling
- MeSH terms
- Adult, Age Factors, Aged, Animals, Cell Differentiation, Cells, Cultured, Female, Humans, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Biomarkers, Immunophenotyping, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Mice, Receptors, CXCR3, Young Adult
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