CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential
De Simone G, Mazza EMC, Cassotta A, Davydov AN, Kuka M, Zanon V, De Paoli F, Scamardella E, Metsger M, Roberto A, Pilipow K, Colombo FS, Tenedini E, Tagliafico E, Gattinoni L, Mavilio D, Peano C, Price DA, Singh SP, Farber JM, Serra V, Cucca F, Ferrari F, Orru V, Fiorillo E, Iannacone M, Chudakov DM, Sallusto F, Lugli E (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 203
Pages Range: 3179-3189
Journal Issue: 12
Abstract
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.
Involved external institutions
Istituto Clinico Humanitas
Italy (IT)
Central European Institute of Technology (CEITEC)
Czech Republic (CZ)
Università degli Studi di Modena e Reggio Emilia (UNIMORE)
Italy (IT)
National Cancer Institute (NCI)
United States (USA) (US)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Cardiff University
United Kingdom (GB)
US National Institutes of Health (NIH)
United States (USA) (US)
IFOM - FIRC Institute of Molecular Oncology
Italy (IT)
San Rafaele Scientific Institute
Italy (IT)
Institute for Research in Biomedicine
Switzerland (CH)
Italy (IT)
Central European Institute of Technology (CEITEC)
Czech Republic (CZ)
Università degli Studi di Modena e Reggio Emilia (UNIMORE)
Italy (IT)
National Cancer Institute (NCI)
United States (USA) (US)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Cardiff University
United Kingdom (GB)
US National Institutes of Health (NIH)
United States (USA) (US)
IFOM - FIRC Institute of Molecular Oncology
Italy (IT)
San Rafaele Scientific Institute
Italy (IT)
Institute for Research in Biomedicine
Switzerland (CH)
How to cite
APA:
De Simone, G., Mazza, E.M.C., Cassotta, A., Davydov, A.N., Kuka, M., Zanon, V.,... Lugli, E. (2019). CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential. Journal of Immunology, 203(12), 3179-3189. https://doi.org/10.4049/jimmunol.1901072
MLA:
De Simone, Gabriele, et al. "CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential." Journal of Immunology 203.12 (2019): 3179-3189.
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