Various combinations of techniques have been used to functionally characterize lymphoid populations. In Immunity, Davis and colleagues use the single-cell mass spectrometry technique CyTOF to provide a comprehensive picture of CD8+ T cell phenotypic and functional diversity. Using heavy metal isotope–labeled antibodies and tetramers of peptide and major histocompatibility complex, the authors survey various functional attributes, such as intracellular cytokines, degranulation, cytotoxic granule components and T cell antigen receptor specificity, to examine the relationship between surface-marker phenotypes and the function of T cells in the context of their specificity for epitopes of influenza virus, cytomegalovirus and Epstein-Barr virus. They use principal-component analysis to simultaneously analyze and visualize such a large data set. Their analysis suggests that CD8+ T cells have a greater degree of functional and phenotypic complexity than previously appreciated, along a continuum of differentiation and maturation stages that can vary depending on the antigen specificity of the cells.

Immunity 36, 142–152 (2012)