The aorta can act as a site of naïve CD4+ T-cell priming
Neil MacRitchieGianluca GrassiaJonathan NoonanJennifer E. ColeCatherine E. HughesJuliane SchroederRobert A. BensonClément CochainAlma ZerneckeTomasz J. GuzikPaul GarsideClaudia MonacoPasquale Maffia
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Abstract:
Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood.Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion.Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression.Keywords:
Priming (agriculture)
Homing (biology)
Objective To explore the homing regularity of different doses of bone marrow cell transplantation.Method An allogeneic mouse model was used in this study.The homing status of different dose groups from the first day to the forth day after transplantation were observed.Results The rate of positive cells in bone marrow and spleen:differences among four groups was not significant.The rate of positive cells of third day was highest among four days (P<0.01).A phenomenon that homing-mobilization-rehoming could be observed.The homing efficiency:low dose groups were higher than that high dose groups (P<0.01).Conclusion The homing efficiency of low dose groups is higher than that of the high dose groups in certain range,the routine method of transplanting a large quantities cells by a single injection may be an waste.
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Transplanting
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Study of marked adult walleyes returning to a spawning site in Many Point Lake, northern Minnesota, showed evidence of homing behavior rather than a strictly random return in successive years. The homing behavior, however, was not shown by the majority of the fish, and among those which evinced homing behavior the pattern of return was irregular. Possible causes of variation in homing in different years and circumstances which could produce an apparent homing effect are discussed.
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It is found that the homing mechanism is not unified yet by review of bone marrow mesenchymal stem cells(BMSCs) homing mechanism and influencing factors.It can improve BMSCs transplant niche and increase homing rates by combining blood-activating and stasis-eliminating and Yang-warming and Kidney essence-replenishing methods.Autors proposed that we can combine meridian viscera theory and the effective formulae for resolving the problem of homing.
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Regenerative Medicine
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Background The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naïve T cells. Responses included several CD4+ and CD8+ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4+ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4+ T cell depletion which renders the newly activated HIV-specific CD4+ T cells prime targets for elimination. Conclusion Our studies highlight the ability of DCs to efficiently prime naïve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
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Ex vivo
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Mesenchymal stromal cells (MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC homing has been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.
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Cell therapy
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Hematopoietic stem cell
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Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to "home" to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and the in vivo environment facilitate and are required for the migration of MSCs to the site of insult or injury in vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.
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Cell therapy
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Objective To explore the homing regularity of different doses of bone marrow cell transplantation.Method An allogeneic mouse model was used in this study.The homing status of different dose groups from the first day to the forth day after transplantation were observed.Results The rate of positive cells in bone marrow and spleen:differences among four groups was not significant.The rate of positive cells of third day was highest among four days ( P 0 01).A phenomenon that homing\|mobilization\|rehoming could be observed.The homing efficiency:low dose groups were higher than that high dose groups ( P 0.01).Conclusion The homing efficiency of low dose groups is higher than that of the high dose groups in certain range,the routine method of transplanting a large quantities cells by a single injection may be an waste.
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Abstract Against a subset of human cancers, vigorous tumor-specific CD8+ T cell responses can develop either spontaneously or upon allogeneic transplantation. However, the parameters that determine the induction of such pronounced anti-tumor immunity remain ill defined. To dissect the conditions required for the induction of high magnitude T cell responses, we have developed a murine model system in which tumor-specific T cell responses can be monitored directly ex vivo by MHC tetramer technology. In this model, tumor challenge of naive mice with Ag-bearing tumor cells results in a massive Ag-specific T cell response, followed by CD8+ T cell-dependent tumor rejection. We have subsequently used this model to assess the contribution of direct priming and cross-priming in the induction of tumor immunity in a well-defined system. Our results indicate that direct priming of T cells and Ag cross-priming are redundant mechanisms for the induction of tumor-specific T cell immunity. Moreover, T cell responses that arise as a consequence of Ag cross-presentation can occur in the absence of CD4+ T cell help and are remarkably robust.
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Lymphocyte homing receptor
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