Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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-γ (IFN-γ) 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-γ amounts preserved a quantitative memory for both probability and magnitude of IFN-γ 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-γ 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.

Original publication




Journal article



Publication Date





108 - 122


Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, 10117 Berlin, Germany; German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany.


Th1 Cells, Cells, Cultured, Macrophages, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, Mice, Salmonella typhimurium, Lymphocytic choriomeningitis virus, Salmonella Infections, Lymphocytic Choriomeningitis, T-Box Domain Proteins, Receptors, Interferon, Colony Count, Microbial, Viral Load, Lymphocyte Activation, Cell Differentiation, Immunologic Memory, Gene Expression Regulation, Cell Lineage, Models, Theoretical, Interferon-gamma, Single-Cell Analysis