| First Author | Helmstetter C | Year | 2015 |
| Journal | Immunity | Volume | 42 |
| Issue | 1 | Pages | 108-22 |
| PubMed ID | 25607461 | Mgi Jnum | J:259034 |
| Mgi Id | MGI:6141889 | Doi | 10.1016/j.immuni.2014.12.018 |
| Citation | Helmstetter C, et al. (2015) Individual T helper cells have a quantitative cytokine memory. Immunity 42(1):108-22 |
| abstractText | The probabilistic expression of cytokine genes in differentiated T helper (Th) cell populations remains ill defined. By single-cell analyses and mathematical modeling, we show that one stimulation featured stable cytokine nonproducers as well as stable producers with wide cell-to-cell variability in the magnitude of expression. Focusing on interferon-gamma (IFN-gamma) expression by Th1 cells, mathematical modeling predicted that this behavior reflected different cell-intrinsic capacities and not mere gene-expression noise. In vivo, Th1 cells sort purified by secreted IFN-gamma amounts preserved a quantitative memory for both probability and magnitude of IFN-gamma re-expression for at least 1 month. Mechanistically, this memory resulted from quantitatively distinct transcription of individual alleles and was controlled by stable expression differences of the Th1 cell lineage-specifying transcription factor T-bet. Functionally, Th1 cells with graded IFN-gamma production competence differentially activated Salmonella-infected macrophages for bacterial killing. Thus, individual Th cells commit to produce distinct amounts of a given cytokine, thereby generating functional intrapopulation heterogeneity. |
