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

Abstract:

: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 × 10(4) 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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Ma C,Fan R,Ahmad H,Shi Q,Comin-Anduix B,Chodon T,Koya RC,Liu CC,Kwong GA,Radu CG,Ribas A,Heath JR

doi

10.1038/nm.2375

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

738-43

issue

6

eissn

1078-8956

issn

1546-170X

pii

nm.2375

journal_volume

17

pub_type

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