Philippe Bousso

..Therefore, the contribution of a T cell clone to the immune response is mostly determined by the time of its entry into the immune repertoire, i.e., the time of first cell division after antigen encounter...

..Emphasis is placed on the role of the naive alphabeta T cell repertoire and on the dynamics of individual Ag-specific T cell clones during the successive phases of an immune response...

..We conclude that, at least for this set of epitopes, the CTL hierarchy is not controlled by the same parameters in a primary vs a secondary response...

..This Review focuses on how this emerging field is changing our perception of T-cell activation by DCs...

..Resolving thymocyte behavior at the single-cell level should help to clarify the mode of trafficking in the thymus and identify the spatio-temporal aspects of thymic selection events...

..Taken together, our results identify the cellular behaviors that promote an efficient CD8+ T cell response in the lymph node...

..Altogether, our results offer mechanistic insight into how NK cells and CTLs can exert cytotoxic activity with remarkably different contact dynamics...

..Our results support a model in which CD4 help operates rapidly, in part by favoring CD8 T cells recruitment around those DCs that are the most competent for priming...

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..Thus, the early set of T cell-DC interactions in lymph nodes largely contribute to the heterogeneity of T cell responses through the generation of functionally divergent clonal progenies...

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..These results establish the importance of prolonged T cell-DC interactions for efficient CD4(+) T cell activation in vivo...

..That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues...

..Our results suggest that type I IFNs produced following viral infection simultaneously target accessory cells for IL-15 transpresentation and NK cells themselves and that these two pathways cooperate for NK cell priming...

..The ability to visualize when, where, and how tumor cells are killed in vivo offers new perspectives for understanding how immune effectors survey cancer cells and how local tumor microenvironments may subvert immune responses...

..In this review we summarize what we have learned so far and point out areas for future investigation using this approach...

..Intravital two-photon imaging is a powerful tool to study the migration and cell interactions of immune cells such as NK and DC in physiological settings...

..This method should provide new insights into the regulation of lymphocyte migration and cell-cell interactions in various immunological contexts...

..Our results identify the diversity and dynamics of thymocyte interactions during positive selection...

..Thus, repeated encounters with Ag-bearing DCs can occur in vivo and modulate CD4 T cell differentiation programs...

..As illustrated here, the DISC approach should provide unique opportunities to link immune cell behavior to phenotype and function in vivo...

..Our results thus demonstrate that CD4(+) T cells can exert their protective activity by engaging a minority of infected cells...

..Furthermore, we provide a dynamic look at immunological kinapses and synapses in lymph nodes and suggest the existence of distinct patterns of LAT redistribution during antigen recognition...

..Thus, disparities in the dynamics of T cell contacts with infected cells and local variation in T cell access to infected cells are important elements of the host-pathogen interplay...

..Our results offer insight into a poorly explored phase of immunity and provide a versatile methodology to study apoptosis during the development or function of a variety of immune cells in vivo...

..Recent studies have begun to depict the cellular orchestration of T cell priming and to analyze the way it could influence the outcome of T cell responses...

..These approaches could be readily adapted to other fluorescent fusion proteins, tissues and biological questions...

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..Our data suggest the existence of a Qa-1-recognizing structure on a large subpopulation of murine NK cells that may be similar to the human CD94/NKG2 heterodimeric complex...

..Thus, complementary signals mediated by recognition of stress ligands and tumor-specific Abs may contribute to the efficacy of NK cells during mAb therapy...

..Our results identify SCS macrophages as primary mediators of NK cell activation in response to lymph-borne viral particles suggesting that they act as early sensors of local infection or delivery of viral-based vaccines...

..These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt(+) T cells and Th17 cells...

..In this review, we discuss the implications of thymocyte motility for T-cell repertoire selection and for the mechanisms that determine the spatial organization of thymocyte subsets within the thymus...

..These results suggest that numerous low-affinity self-specific T cells persist in the periphery and show that a deleting ligand can specifically narrow the structural diversity of the TCR repertoire...

..In mice and probably humans, we estimate that a minimum of 85 DCs are required to initiate a T-cell response when starting from precursor frequency of 10(-6). Our results have implications for the rational design of DC-based vaccines...

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..We review here our recent understanding of NK cell interactions in vivo at steady state, during inflammation, and during tumor elimination, emphasizing the similarities and differences with T cells...

..These findings imply that long-lived Ag is critical for efficient vaccination protocols in which the CD8(+) T cell response is helper-dependent...

..Our results suggest that immunotherapy trials involving new peptides should be pursued with caution and should include a careful monitoring of the T cell response...