title: Modeling leukocyte-leukocyte non-contact interactions in a lymph node.
abstract: The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.
authors.affiliation: Dipartimento di Fisica, Università degli studi di Milano-Bicocca, Milano, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gritti
authors.forename: Michele
authors.initials: M
authors.lastname: Caccia
authors.forename: Laura
authors.initials: L
authors.lastname: Sironi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Collini
authors.forename: Laura
authors.initials: L
authors.lastname: D'Alfonso
authors.forename: Francesca
authors.initials: F
authors.lastname: Granucci
authors.forename: Ivan
authors.initials: I
authors.lastname: Zanoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chirico
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma