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Suited to a T

Sorting out T-cell functional and phenotypic heterogeneity depends on studying single cells.

Written byKelly Rae Chi
| 8 min read

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EYES ON Ts: Using intravital microscopy researchers can take an in vivo look at T cells (green and red) infiltrating a mouse tumor.IMAGE BY FRANCESCO MARANGONIActivated T cells are a diverse and ever-changing crew. What gives this type of white blood cell the ability to stamp out infection is also what makes it complicated to study. T cells express receptors that respond to specific antigens. Not only different subsets of  T cells, but individual T cells, can react to the same antigen in different ways—for example, by rapidly expanding and differentiating, by releasing distinct sets of cytokines at certain times, or by killing other cells. And, influenced by their past and present experiences, they can change their behavior over the course of months or years.

Because T cells are so flexible in form and function, and are in a constant state of transition, researchers are realizing that extracting them from blood, mashing them together, and analyzing their overall gene expression and other characteristics doesn’t capture their nuances. A more detailed analysis might well reveal clues for improving immune monitoring and developing new therapies.

Technologies that track T cells on the single-cell level are beginning to resolve these cells’ heterogeneity and to show how T-cell populations shift through their continuum of states. “There’s a growing sense that we need to understand how individual T cells behave,” says Ton Schumacher, group leader in immunology at The Netherlands Cancer Institute in Amsterdam. Different single-cell-level techniques for doing so each bring unique angles to ...

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