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CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential

De Simone, Gabriele, Mazza, Emilia M. C., Cassotta, Antonino, Davydov, Alexey N., Kuka, Mirela, Zanon, Veronica, De Paoli, Federica, Scamardella, Eloise, 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 and Lugli, Enrico 2019. CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential. Journal of Immunology 203 (12) , pp. 3179-3189. 10.4049/jimmunol.1901072

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 3 January 2020
Date of Acceptance: 16 October 2019
Last Modified: 17 Jan 2020 11:30

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