Journal
IMMUNITY
Volume 36, Issue 1, Pages 142-152Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2012.01.002
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Funding
- NIH [U19-AI057229, U19-AI090019]
- Bill and Melinda Gates Foundation
- Howard Hughes Medical Institute
- American Cancer Society
- Damon Runyon Postdoctoral Fellowship [DRG-2017-09]
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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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