Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Transforming a traditional commons-based seed system through collaborative networks of farmer seed-cooperatives and public breeding programs: the case of sorghum in Mali

Malian farmers’ traditional system for managing seed of sorghum, an indigenous crop of vital importance for food security and survival, can be conceptualized as a commons. Although this system maintains a wide range of varieties and helps ensure access to seed, its ability to create and widely disseminate new varieties to meet evolving opportunities and challenges is limited. A network of farmer groups, public breeding programs, and development organizations collaborating in decentralized creation and dissemination of sorghum varieties in Mali is examined regarding (1) how the network developed and what activities it conducts; (2) the resulting varietal diversity, varietal performance and organizational models; and (3) the elements of the traditional seed system that were maintained, strengthened or transformed. A single-case study approach was used that relies on published literature, official catalogues of released varieties and a database of farmer seed-cooperative requests for foundation seed. The functioning of the network and its varietal-, seed-, and organizational- outcomes are documented and the elements of the traditional sorghum seed system that are maintained or strengthened are analyzed. The evolution of the network’s reliance on commoning as a social process and its strengthening of core Seed Commons features are discussed with a view to the network’s contributions to targeted development outcomes and potential replicability. The case demonstrates how creating a framework for collaboration, enabling actors and organizations to take on collective responsibility while maintaining distributed decision-making at local level, opens opportunities for transforming farming- and food-systems towards sustainability and resilience