A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells.

Autor: Chao Ma, Rong Fan, Ahmad, Habib, Qihui Shi, Comin-Anduix, Begonya, Chodon, Thinle, Koya, Richard C., Chao-Chao Liu, Kwong, Gabriel A., Radu, Caius G., Ribas, Antoni, Heath, James R.
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Zdroj: Nature Medicine; Jun2011, Vol. 17 Issue 6, p738-743, 6p, 1 Chart, 4 Graphs
Abstrakt: Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1 × 104 cells) and quantitative measurements of secreted proteins from single cells. We validated the platform by assessment of multiple inflammatory cytokines from lipopolysaccharide (LPS)-stimulated human macrophages and comparison to standard immunotechnologies. We applied the platform toward the ex vivo quantification of T cell polyfunctional diversity via the simultaneous measurement of a dozen effector molecules secreted from tumor antigen-specific cytotoxic T lymphocytes (CTLs) that were actively responding to tumor and compared against a cohort of healthy donor controls. We observed profound, yet focused, functional heterogeneity in active tumor antigen-specific CTLs, with the major functional phenotypes quantitatively identified. The platform represents a new and informative tool for immune monitoring and clinical assessment. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index