Immunity or tolerance: opposite outcomes of microchimerism from skin grafts.

Abstract:

:Solid organ transplants contain small numbers of leukocytes that can migrate into the host and establish long-lasting microchimerism. Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. Using skin from mutant mice deficient for leukocyte subsets, we found that donor T-cell chimerism is a 'double-edged sword' that can result in very different outcomes depending on the host's immunological maturity and the antigenic disparities involved. In immunologically mature hosts, chimerism resulted in immunity and stronger graft rejection. In immature hosts, it resulted in tolerance to the chimeric T cells, but not to graft antigens not expressed by the chimeric cells. Clinical efforts aimed at augmenting chimerism to induce tolerance must take into account the maturation state of host T cells, the type of chimerism produced by each organ and the antigenic disparities involved, lest the result be increased rejection rather than tolerance.

journal_name

Nat Med

journal_title

Nature medicine

authors

Anderson CC,Matzinger P

doi

10.1038/83393

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

80-7

issue

1

eissn

1078-8956

issn

1546-170X

journal_volume

7

pub_type

杂志文章
  • Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania.

    abstract::Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3221

    authors: Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DS

    更新日期:2013-07-01 00:00:00

  • Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.

    abstract::Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4421

    authors: Huot N,Jacquelin B,Garcia-Tellez T,Rascle P,Ploquin MJ,Madec Y,Reeves RK,Derreudre-Bosquet N,Müller-Trutwin M

    更新日期:2017-11-01 00:00:00

  • Chip-NMR biosensor for detection and molecular analysis of cells.

    abstract::Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify mole...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.1711

    authors: Lee H,Sun E,Ham D,Weissleder R

    更新日期:2008-08-01 00:00:00

  • Developing neoantigen-targeted T cell-based treatments for solid tumors.

    abstract::Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting 'neoantigens'-the somatic mutations expressed only by tumor cells-might...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/s41591-019-0596-y

    authors: Yamamoto TN,Kishton RJ,Restifo NP

    更新日期:2019-10-01 00:00:00

  • GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes.

    abstract::GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1097-1096

    authors: Stenbit AE,Tsao TS,Li J,Burcelin R,Geenen DL,Factor SM,Houseknecht K,Katz EB,Charron MJ

    更新日期:1997-10-01 00:00:00

  • Interstitial cells of Cajal generate a rhythmic pacemaker current.

    abstract::Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagat...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0798-848

    authors: Thomsen L,Robinson TL,Lee JC,Farraway LA,Hughes MJ,Andrews DW,Huizinga JD

    更新日期:1998-07-01 00:00:00

  • Induction of specific transplantation tolerance across xenogeneic barriers in the T-independent immune compartment.

    abstract::After transplantation of primarily vascularized xenografts (Xgs), T-independent mechanisms may lead to Xg rejection before T-cell activation even takes place. The possibility of achieving T-independent xenotolerance was evaluated in nude rats that normally reject hamster cardiac Xgs within 4 days by non-T cell-mediate...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0298-173

    authors: Lin Y,Goebels J,Xia G,Ji P,Vandeputte M,Waer M

    更新日期:1998-02-01 00:00:00

  • Serum levels of the iron binding protein p97 are elevated in Alzheimer's disease.

    abstract::Alzheimer's disease is a progressive and incurable disease whose prevalence increases dramatically with age. A biochemical marker for monitoring the onset and progression of the disease would be a valuable tool for disease management. In addition, such a marker might be used as an end point in clinical intervention pr...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1196-1230

    authors: Kennard ML,Feldman H,Yamada T,Jefferies WA

    更新日期:1996-11-01 00:00:00

  • Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

    abstract::Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs)...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0116-5

    authors: Cañadas I,Thummalapalli R,Kim JW,Kitajima S,Jenkins RW,Christensen CL,Campisi M,Kuang Y,Zhang Y,Gjini E,Zhang G,Tian T,Sen DR,Miao D,Imamura Y,Thai T,Piel B,Terai H,Aref AR,Hagan T,Koyama S,Watanabe M,Baba H,

    更新日期:2018-08-01 00:00:00

  • Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

    abstract::Immune sensing of a microbe occurs via multiple receptors. How signals from different receptors are coordinated to yield a specific immune response is poorly understood. We show that two pathogen recognition receptors, Toll-like receptor 2 (TLR2) and dectin-1, recognizing the same microbial stimulus, stimulate distinc...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.1925

    authors: Manicassamy S,Ravindran R,Deng J,Oluoch H,Denning TL,Kasturi SP,Rosenthal KM,Evavold BD,Pulendran B

    更新日期:2009-04-01 00:00:00

  • Clinical microfluidics for neutrophil genomics and proteomics.

    abstract::Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by compariso...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2205

    authors: Kotz KT,Xiao W,Miller-Graziano C,Qian WJ,Russom A,Warner EA,Moldawer LL,De A,Bankey PE,Petritis BO,Camp DG 2nd,Rosenbach AE,Goverman J,Fagan SP,Brownstein BH,Irimia D,Xu W,Wilhelmy J,Mindrinos MN,Smith RD,Davis RW

    更新日期:2010-09-01 00:00:00

  • Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets.

    abstract::Osteopontin (Opn) is important for T helper type 1 (T(H)1) immunity and autoimmunity. However, the role of this cytokine in T(H)2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1580

    authors: Xanthou G,Alissafi T,Semitekolou M,Simoes DC,Economidou E,Gaga M,Lambrecht BN,Lloyd CM,Panoutsakopoulou V

    更新日期:2007-05-01 00:00:00

  • Sensory feedback restoration in leg amputees improves walking speed, metabolic cost and phantom pain.

    abstract::Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1-4. The lack of physiological feedback from the remaining extremity to th...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0567-3

    authors: Petrini FM,Bumbasirevic M,Valle G,Ilic V,Mijović P,Čvančara P,Barberi F,Katic N,Bortolotti D,Andreu D,Lechler K,Lesic A,Mazic S,Mijović B,Guiraud D,Stieglitz T,Alexandersson A,Micera S,Raspopovic S

    更新日期:2019-09-01 00:00:00

  • Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

    abstract::One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/78682

    authors: Bard F,Cannon C,Barbour R,Burke RL,Games D,Grajeda H,Guido T,Hu K,Huang J,Johnson-Wood K,Khan K,Kholodenko D,Lee M,Lieberburg I,Motter R,Nguyen M,Soriano F,Vasquez N,Weiss K,Welch B,Seubert P,Schenk D,Yednock

    更新日期:2000-08-01 00:00:00

  • Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response.

    abstract::We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1358

    authors: Manno CS,Pierce GF,Arruda VR,Glader B,Ragni M,Rasko JJ,Ozelo MC,Hoots K,Blatt P,Konkle B,Dake M,Kaye R,Razavi M,Zajko A,Zehnder J,Rustagi PK,Nakai H,Chew A,Leonard D,Wright JF,Lessard RR,Sommer JM,Tigges M,S

    更新日期:2006-03-01 00:00:00

  • Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.

    abstract::Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) wit...

    journal_title:Nature medicine

    pub_type: 临床试验,杂志文章

    doi:10.1038/s41591-018-0295-0

    authors: Cideciyan AV,Jacobson SG,Drack AV,Ho AC,Charng J,Garafalo AV,Roman AJ,Sumaroka A,Han IC,Hochstedler MD,Pfeifer WL,Sohn EH,Taiel M,Schwartz MR,Biasutto P,Wit W,Cheetham ME,Adamson P,Rodman DM,Platenburg G,Tome MD,

    更新日期:2019-02-01 00:00:00

  • The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.

    abstract::The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamina...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm945

    authors: Sheehy AM,Gaddis NC,Malim MH

    更新日期:2003-11-01 00:00:00

  • Environmental shaping of the microbiome.

    abstract:: ...

    journal_title:Nature medicine

    pub_type: 评论,杂志文章

    doi:10.1038/s41591-018-0286-1

    authors: Stower H

    更新日期:2018-12-01 00:00:00

  • Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.

    abstract::Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered a potent, drug-inducible CD40 (iCD40) receptor that permits te...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1183

    authors: Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

    更新日期:2005-02-01 00:00:00

  • NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages.

    abstract::Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanis...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4153

    authors: Moon JS,Nakahira K,Chung KP,DeNicola GM,Koo MJ,Pabón MA,Rooney KT,Yoon JH,Ryter SW,Stout-Delgado H,Choi AM

    更新日期:2016-09-01 00:00:00

  • Conversion of vascular endothelial cells into multipotent stem-like cells.

    abstract::Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2252

    authors: Medici D,Shore EM,Lounev VY,Kaplan FS,Kalluri R,Olsen BR

    更新日期:2010-12-01 00:00:00

  • Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.

    abstract::Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparu...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/71582

    authors: Beeson JG,Rogerson SJ,Cooke BM,Reeder JC,Chai W,Lawson AM,Molyneux ME,Brown GV

    更新日期:2000-01-01 00:00:00

  • Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions.

    abstract::Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal cen...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2426

    authors: Chung Y,Tanaka S,Chu F,Nurieva RI,Martinez GJ,Rawal S,Wang YH,Lim H,Reynolds JM,Zhou XH,Fan HM,Liu ZM,Neelapu SS,Dong C

    更新日期:2011-07-24 00:00:00

  • Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity.

    abstract::Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interacti...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3735

    authors: Arruda AP,Pers BM,Parlakgül G,Güney E,Inouye K,Hotamisligil GS

    更新日期:2014-12-01 00:00:00

  • Inducible cyclooxygenase may have anti-inflammatory properties.

    abstract::Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes; inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases. Here we present evidence that COX 2 may have anti-infla...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/9550

    authors: Gilroy DW,Colville-Nash PR,Willis D,Chivers J,Paul-Clark MJ,Willoughby DA

    更新日期:1999-06-01 00:00:00

  • Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia.

    abstract::Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2819

    authors: Kentsis A,Reed C,Rice KL,Sanda T,Rodig SJ,Tholouli E,Christie A,Valk PJ,Delwel R,Ngo V,Kutok JL,Dahlberg SE,Moreau LA,Byers RJ,Christensen JG,Vande Woude G,Licht JD,Kung AL,Staudt LM,Look AT

    更新日期:2012-07-01 00:00:00

  • IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.

    abstract::Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining loc...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1710

    authors: Aujla SJ,Chan YR,Zheng M,Fei M,Askew DJ,Pociask DA,Reinhart TA,McAllister F,Edeal J,Gaus K,Husain S,Kreindler JL,Dubin PJ,Pilewski JM,Myerburg MM,Mason CA,Iwakura Y,Kolls JK

    更新日期:2008-03-01 00:00:00

  • Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial.

    abstract::Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761 ), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two ...

    journal_title:Nature medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1038/s41591-020-1085-z

    authors: van Dijk N,Gil-Jimenez A,Silina K,Hendricksen K,Smit LA,de Feijter JM,van Montfoort ML,van Rooijen C,Peters D,Broeks A,van der Poel HG,Bruining A,Lubeck Y,Sikorska K,Boellaard TN,Kvistborg P,Vis DJ,Hooijberg E,Schumac

    更新日期:2020-12-01 00:00:00

  • Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network.

    abstract::Computerized electrocardiogram (ECG) interpretation plays a critical role in the clinical ECG workflow1. Widely available digital ECG data and the algorithmic paradigm of deep learning2 present an opportunity to substantially improve the accuracy and scalability of automated ECG analysis. However, a comprehensive eval...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0268-3

    authors: Hannun AY,Rajpurkar P,Haghpanahi M,Tison GH,Bourn C,Turakhia MP,Ng AY

    更新日期:2019-01-01 00:00:00

  • Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia.

    abstract::Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1-3. Previously, we reported a clinical case of complete sensorimotor par...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0175-7

    authors: Gill ML,Grahn PJ,Calvert JS,Linde MB,Lavrov IA,Strommen JA,Beck LA,Sayenko DG,Van Straaten MG,Drubach DI,Veith DD,Thoreson AR,Lopez C,Gerasimenko YP,Edgerton VR,Lee KH,Zhao KD

    更新日期:2018-11-01 00:00:00