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.

• MeSH
• Lymphocyte Activation immunology   MeSH
• Biomarkers MeSH
• Cell Differentiation immunology   MeSH
• CD8-Positive T-Lymphocytes immunology   metabolism   MeSH
• Adult MeSH
• Immunophenotyping MeSH
• Immunologic Memory MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Mice MeSH
• Receptors, CXCR3 metabolism   MeSH
• Aged MeSH
• T-Lymphocyte Subsets immunology   metabolism   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Mice MeSH
• Aged MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Intramural MeSH
• Names of Substances
• Biomarkers MeSH
• CXCR3 protein, human MeSH Browser
• Receptors, CXCR3 MeSH