Killer artificial antigen-presenting cells deplete alloantigen-specific T cells in a murine model of alloskin transplantation

Shen, Chuanlai; He, Yong; Cheng, Kai; Zhang, Daoping; Miao, Shenwei; Zhang, Aifeng; Meng, Fanliang; Miao, Fengqin; Zhang, Jianqiong

doi:10.1016/j.imlet.2011.04.002

Cited by 28 publications

(20 citation statements)

References 40 publications

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“…DCs are able to present innocuous self and non-self antigens in a manner that promotes tolerance [8]. The predominant mechanism by which DCs induce and maintain peripheral tolerance involves the generation of Tregs from naïve T cells, the expansion of pre-existing Tregs, the production of IL-10 and other immunomodulatory cytokines, and the promotion of T cell anergy or depletion [11, 12]. …”

Section: Introductionmentioning

confidence: 99%

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

2017

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BackgroundA vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health.MethodsThis paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA).ResultsIn addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction.ConclusionsA better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.

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Section: Introductionmentioning

confidence: 99%

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

2017

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“…Recently, Shen et al have reported the successful in vivo usage of KaAPC utilizing 5 μm latex beads conjugated to anti-Fas (clone Jo2) and anti-His/H2-K b -TRP2 11 . We have been able to show that the general concept of artificial antigen-presenting Cells (aAPC) can be successfully transferred from μm sized to nm sized particles 12 and that functionality is influenced by particle geometry 13 .…”

Section: Discussionmentioning

confidence: 99%

Killer Artificial Antigen Presenting Cells (KaAPC) for Efficient <em>In Vitro</em> Depletion of Human Antigen-specific T Cells

Schütz

Schneck

Oelke

2014

JoVE

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Current treatment of T cell mediated autoimmune diseases relies mostly on strategies of global immunosuppression, which, in the long term, is accompanied by adverse side effects such as a reduced ability to control infections or malignancies. Therefore, new approaches need to be developed that target only the disease mediating cells and leave the remaining immune system intact. Over the past decade a variety of cell based immunotherapy strategies to modulate T cell mediated immune responses have been developed. Most of these approaches rely on tolerance-inducing antigen presenting cells (APC). However, in addition to being technically difficult and cumbersome, such cell-based approaches are highly sensitive to cytotoxic T cell responses, which limits their therapeutic capacity. Here we present a protocol for the generation of non-cellular killer artificial antigen presenting cells (KaAPC), which allows for the depletion of pathologic T cells while leaving the remaining immune system untouched and functional. KaAPC is an alternative solution to cellular immunotherapy which has potential for treating autoimmune diseases and allograft rejections by regulating undesirable T cell responses in an antigen specific fashion.

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“…When co-cultured with T cell populations, these aAPCs were able to promote antigen specific T cell depletion in a FasL dependent mechanism [104]. In another study, “killer aAPCs” were shown prolong skin allograft survival (in a mouse model) via the deletion of antigen specific, alloreactive T cells [105]. Given these promising results, it will be interesting to see how these therapies translate to solid organ transplantation.…”

Section: Biomimetic Drug Deliverymentioning

confidence: 99%

Micro and nanoparticle drug delivery systems for preventing allotransplant rejection

Fisher

Acharya

Little

2015

Clinical Immunology

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Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation.

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Killer artificial antigen-presenting cells deplete alloantigen-specific T cells in a murine model of alloskin transplantation

Cited by 28 publications

References 40 publications

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases

Killer Artificial Antigen Presenting Cells (KaAPC) for Efficient <em>In Vitro</em> Depletion of Human Antigen-specific T Cells

Micro and nanoparticle drug delivery systems for preventing allotransplant rejection

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