Polyfunctional T Cells

Science Signaling  07 Feb 2012:
Vol. 5, Issue 210, pp. ec42
DOI: 10.1126/scisignal.2002929

In addition to being classified on the basis of cell-surface markers, including CD4, CD8, and various chemokine receptors, T cells are also cataloged, based on the types of cytokines that they produce, into different functional subsets: T helper 1 (TH1), TH2, and TH17 cells, for example. Those T cells that produce multiple cytokines, so-called “polyfunctional” T cells, provide a more effective immune response to a pathogen than do cells that produce only a single cytokine (see commentary by Haining). Because most studies of T cell functionality are based on end-point analysis of populations of activated T cells, whether polyfunctional cells produce multiple cytokines sequentially or simultaneously is unclear. Thus, Han et al. devised a system to monitor the real-time secretion of cytokines by individual cells. The authors cultured human T cells individually in nanowells, analyzed their cell-surface markers, activated the cells in a T cell receptor (TCR)–independent manner, and then repeatedly sampled the culture medium to measure the concentrations of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor–α (TNF-α) that the cells secreted. Most T cells that produced multiple cytokines did so sequentially rather than simultaneously. Mathematical analysis showed that the patterns of serial secretion exhibited by the cells were programmed rather than random. Furthermore, cells in different differentiation states had distinct patterns of secretion. Thus, naïve CD4+ T cells exhibited a secretion pattern that could be distinguished from that of effector memory cells, for example. Finally, to more closely model physiological T cell activation, the authors incubated cells with beads coated with TCR-activating antibodies and found that cells exhibited qualitatively similar patterns of cytokine secretion as were observed in the earlier experiments. As Haining discusses, these data suggest that to effectively characterize an immune response, one must determine how the phenotypes of individual T cells within a population change over time.

Q. Han, N. Bagheri, E. M. Bradshaw, D. A. Hafler, D. A. Lauffenburger, J. C. Love, Polyfunctional responses by human T cells result from sequential release of cytokines. Proc. Natl. Acad. Sci. U.S.A.109, 1607–1612 (2012). [Abstract] [Full Text]

W. N. Haining, Travels in time: Assessing the functional complexity of T cells. Proc. Natl. Acad. Sci. U.S.A.109, 1359–1360 (2012). [Full Text]