CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential.
Gabriele De SimoneEmilia M C MazzaAntonino CassottaAlexey N DavydovMirela KukaVeronica ZanonFederica De PaoliEloise ScamardellaMaria MetsgerAlessandra RobertoKarolina PilipowFederico Simone ColomboElena TenediniEnrico TagliaficoLuca GattinoniDomenico MavilioClelia PeanoDavid A PriceSatya P SinghJoshua M FarberValentina SerraFrancesco CuccaFrancesco FerrariValeria OrrùEdoardo FiorilloMatteo IannaconeDmitriy M ChudakovFederica SallustoEnrico LugliPublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- endothelial cells
- regulatory t cells
- dendritic cells
- single cell
- endoplasmic reticulum stress
- stem cells
- oxidative stress
- signaling pathway
- cell death
- type diabetes
- climate change
- transcription factor
- dna methylation
- induced pluripotent stem cells
- metabolic syndrome
- adipose tissue
- cell migration
- antiretroviral therapy
- insulin resistance
- skeletal muscle
- human health
- long non coding rna
- heat shock protein