CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential
| Autor: | Maria Metsger, Eloise Scamardella, Valentina Serra, Elena Tenedini, Alexey N. Davydov, Emilia Maria Cristina Mazza, Karolina Pilipow, Alessandra Roberto, Francesco Ferrari, Joshua M. Farber, Domenico Mavilio, Clelia Peano, David Price, Veronica Zanon, Federico Colombo, Federica Sallusto, Gabriele De Simone, Edoardo Fiorillo, Antonino Cassotta, Dmitriy M. Chudakov, Matteo Iannacone, Enrico Tagliafico, Luca Gattinoni, Valeria Orrù, Enrico Lugli, Federica De Paoli, Mirela Kuka, Satya P. Singh, Francesco Cucca |
|---|---|
| Přispěvatelé: | 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, Lugli, Enrico |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Receptors CXCR3 Immunology chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Lymphocyte Activation CXCR3 Immunophenotyping Mice Young Adult 03 medical and health sciences 0302 clinical medicine T-Lymphocyte Subsets Animals Humans Immunology and Allergy Cytotoxic T cell Cells Cultured Aged Chemistry Effector T-cell receptor Age Factors Cell Differentiation hemic and immune systems Middle Aged Cell biology Clinical and Human Immunology Female Tumor necrosis factor alpha CD5 Immunologic Memory Biomarkers CD8 030215 immunology |
| Zdroj: | The Journal of Immunology The Journal of Immunology Author Choice |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Key Points CXCR3 identifies human naive CD8+ T cells with biased effector potential. Human naive CD8+ T cell subsets are functionally and transcriptionally distinct. Effector potential correlates with the physicochemical attributes of expressed TCRs. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|