Collective versus Single--Particle Motion in Quantum Many--Body Systems: Spreading and its Semiclassical Interpretation

We study the interplay between collective and incoherent single-particle motion in a model of two chains of particles whose interaction comprises a non-integrable part. In the perturbative regime, but for a general form of the interaction, we calculate the spectral density for collective excitations. We obtain the remarkable result that it always has a unique semiclassical interpretation. We show this by a proper renormalization procedure which allows us to map our system to a Caldeira-Leggett--type of model in which the bath is part of the system.Comment: 4 page

Innate type 2 immunity in helminth infection is induced redundantly and acts autonomously following CD11c+ cell depletion

Infection with gastrointestinal helminths generates a dominant type 2 response among both adaptive (Th2) and innate (macrophage, eosinophil, and innate lymphoid) immune cell types. Two additional innate cell types, CD11chigh dendritic cells (DCs) and basophils, have been implicated in the genesis of type 2 immunity. Investigating the type 2 response to intestinal nematode parasites, including Heligmosomoides polygyrus and Nippostrongylus brasiliensis, we first confirmed the requirement for DCs in stimulating Th2 adaptive immunity against these helminths through depletion of CD11chigh cells by administration of diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in mice depleted of basophils by antibody treatment. Th2 responses can be induced by adoptive transfer of DCs, but not basophils, exposed to soluble excretory-secretory products from these helminths. However, innate type 2 responses arose equally strongly in the presence or absence of CD11chigh cells or basophils; thus, in CD11c.DOG mice, the alternative activation of macrophages, as measured by expression of arginase-1, RELM-α, and Ym-1 (Chi3L3) in the intestine following H. polygyrus infection or in the lung following N. brasiliensis infection, was unaltered by depletion of CD11c-expressing DCs and alveolar macrophages or by antibody-mediated basophil depletion. Similarly, goblet cell-associated RELM-β in lung and intestinal tissues, lung eosinophilia, and expansion of innate lymphoid (“nuocyte”) populations all proceeded irrespective of depletion of CD11chigh cells or basophils. Thus, while CD11chigh DCs initiate helminth-specific adaptive immunity, innate type 2 cells are able to mount an autonomous response to the challenge of parasite infection

A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their requirement for homeostatic proliferation of natural killer cells

Dendritic cells (DC) are known to support the activation of natural killer (NK) cells. However, little is known about the role for DC in NK-cell homeostasis. In order to investigate this question, a novel bacterial artificial chromosome transgenic mouse model was generated in which the diphtheria toxin receptor is expressed under the CD11c promoter. In these mice efficient DC depletion can be achieved over prolonged periods of time by multiple injections of diphtheria toxin. We show here that NK cells require DC for full acquisition of effector function in vivo in response to the bacterial-derived TLR ligand CpG. Importantly, DC were found to play an instrumental role for maintaining normal homeostasis of NK cells. This is achieved by IL-15 production by DC, which supports the homeostatic proliferation of NK cells. . There is much known about the molecular mechanisms of NK-cell functions, but the factors influencing NK-cell numbers are only beginning to be elucidated. Mature NK cells were typically thought to be a terminally differentiated population, with a very limited selfrenewal capacity. However, it was recently shown that a small percentage of NK cells actively proliferate in the steady state, resulting in a half life of the NK-cell population of about 17 days SHORT COMMUNICATION Ã These authors contributed equally to this study. Correspondence: Dr. Natalio Garbi e-mail: n. 2776 Importantly, we observe a previously unrecognized role for DC in optimal homeostatic proliferation of NK cells in lymphopenic conditions. In this process, DC-derived IL-15 appears to play an important role. Our data indicate that not only T lymphocytes, but also NK cells require DC for homeostatic proliferation. Results CD11c.DOG mice allow long-term ablation of DC in vivo without toxicity effects In order to study the effect of in vivo interaction between DC and NK cells, a system that permits long-term depletion of DC is required. The diphtheria toxin/diphtheria toxin receptor (DT/DTR) system introduced by Saito et al. Injection of 8 ng/gram body weight (gbw) DT induced depletion of DC (CD11c high MHC class II 1 ) in spleen, lymph nodes, thymus and bone marrow, albeit efficiency of depletion varied in the different organs tested The data shown in Although mice tolerated well 8 ng/gbw for prolonged periods of time, DC depletion was limited to a period of 11-12 days In order to confirm faithful expression of the BAC, we thoroughly examined CD11c expression and depletion of B cells, T cells, NK cells and NKT cells in spleens after 8 ng/gbw DT administration. The minor CD11c hi subpopulations of these cell types were effectively depleted, whereas CD11c int/lo cells were only partially depleted (Supporting Information In conclusion, the new BAC transgenic CD11c.DOG mouse model introduced here allows effective long-term depletion of CD11c 1 cells. DC are required for optimal NK-cell activation and homeostatic proliferation in vivo of NK cells. NK cells were activated by administration of the TLR-9 ligand CpG and the in vivo lytic activity determined by injection of CFSE-labelled tapasin-deficient splenocytes that served as NK targets. CpG administration in mice with a normal DC compartment lead to increased NK cytotoxicity in vivo ( The homeostasis of T cells has been well studied and found to require several factors including the presence of DC, self MHC molecules and the cytokine IL-7 for proliferation and survival ) in DC-depleted CD11c.DOG mice compared with DC-sufficient B6 mice ( DC-derived IL-15 contributes to lymphopenia-induced proliferation of NK cells The cytokine IL-15 has been reported to be crucial for activation and survival of NK cells Concluding remarks In summary, this study introduces a new BAC transgenic CD11c.DTR mouse model for prolonged in vivo depletion of DC by application of DT, without any apparent signs of toxicity. Experiments using this mouse line demonstrated a previously unrecognized role for DC in the homeostasis of NK cells, and showed that local production of IL-15 by DC is required for the maintenance of the NK-cell compartment. Thus, the present study adds an additional function to the long list of DC functions, which so far encompass antigen presentation to and activation of CD4 and CD8 T cells, deletion of T cells and induction of regulatory 1 ) NK cells were quantified 7 days after transfer into irradiated chimeras. Three mice were used in each group. The experiment was repeated three times with similar results. Ã po0.05, Student's t-test

Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation

Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment.DFG grants: (ZE526/4-2, SFB854TP7), Wilhelm Sander Stiftung Germany grant: (2009.022.1), Helmholtz Alliance for Immunotherapy, FCT, Medical Faculty Otto-von-Guericke University PhD grant