[PDF][PDF] Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes
Immunity, 2012•cell.com
Cytotoxic CD8+ T lymphocytes directly kill infected or aberrant cells and secrete
proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis
(cytometry by time-of-flight, or CyTOF) of human CD8+ T cells, we analyzed the expression
of many more proteins than previously possible with fluorescent labels, including surface
markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-
dimensional principal component analysis (3D-PCA) to display phenotypic diversity, we …
proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis
(cytometry by time-of-flight, or CyTOF) of human CD8+ T cells, we analyzed the expression
of many more proteins than previously possible with fluorescent labels, including surface
markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-
dimensional principal component analysis (3D-PCA) to display phenotypic diversity, we …
Summary
Cytotoxic CD8+ T lymphocytes directly kill infected or aberrant cells and secrete proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis (cytometry by time-of-flight, or CyTOF) of human CD8+ T cells, we analyzed the expression of many more proteins than previously possible with fluorescent labels, including surface markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-dimensional principal component analysis (3D-PCA) to display phenotypic diversity, we observed a relatively uniform pattern of variation in all subjects tested, highlighting the interrelatedness of previously described subsets and the continuous nature of CD8+ T cell differentiation. These data also showed much greater complexity in the CD8+ T cell compartment than previously appreciated, including a nearly combinatorial pattern of cytokine expression, with distinct niches occupied by virus-specific cells. This large degree of functional diversity even between cells with the same specificity gives CD8+ T cells a remarkable degree of flexibility in responding to pathogens.
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