Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study.

Abstract:

:We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.

journal_name

Nat Med

journal_title

Nature medicine

authors

Margolick JB,Muñoz A,Donnenberg AD,Park LP,Galai N,Giorgi JV,O'Gorman MR,Ferbas J

doi

10.1038/nm0795-674

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

674-80

issue

7

eissn

1078-8956

issn

1546-170X

journal_volume

1

pub_type

杂志文章
  • Skeletal remodeling in health and disease.

    abstract::The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/nm1593

    authors: Zaidi M

    更新日期:2007-07-01 00:00:00

  • Under pressure: the search for the essential mechanisms of hypertension.

    abstract::High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health because of its associated complications. Despite the high prevalence of essential hypertension and years of research, the basic causes remain obscure. Here I review recent advances in understanding the pathophysi...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/nm.2541

    authors: Coffman TM

    更新日期:2011-11-07 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

  • Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.

    abstract::The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0323-0

    authors: Teixeira VH,Pipinikas CP,Pennycuick A,Lee-Six H,Chandrasekharan D,Beane J,Morris TJ,Karpathakis A,Feber A,Breeze CE,Ntolios P,Hynds RE,Falzon M,Capitanio A,Carroll B,Durrenberger PF,Hardavella G,Brown JM,Lynch AG,Fa

    更新日期:2019-03-01 00:00:00

  • Epidermal growth factor regulates hematopoietic regeneration after radiation injury.

    abstract::The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow serum of mice bearing deletion of Bak and Bax in TIE2-expressing cells in Tie2Cre; Bak1(-/-); Bax(flox/-) m...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3070

    authors: Doan PL,Himburg HA,Helms K,Russell JL,Fixsen E,Quarmyne M,Harris JR,Deoliviera D,Sullivan JM,Chao NJ,Kirsch DG,Chute JP

    更新日期:2013-03-01 00:00:00

  • Local immune monitoring.

    abstract:: ...

    journal_title:Nature medicine

    pub_type: 评论,杂志文章

    doi:10.1038/s41591-018-0332-z

    authors: Stower H

    更新日期:2019-01-01 00:00:00

  • IKK-beta links inflammation to obesity-induced insulin resistance.

    abstract::Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1185

    authors: Arkan MC,Hevener AL,Greten FR,Maeda S,Li ZW,Long JM,Wynshaw-Boris A,Poli G,Olefsky J,Karin M

    更新日期:2005-02-01 00:00:00

  • Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression.

    abstract::Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-bo...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0497-447

    authors: Bargou RC,Jürchott K,Wagener C,Bergmann S,Metzner S,Bommert K,Mapara MY,Winzer KJ,Dietel M,Dörken B,Royer HD

    更新日期:1997-04-01 00:00:00

  • Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3514

    authors: Wang N,Gray M,Lu XH,Cantle JP,Holley SM,Greiner E,Gu X,Shirasaki D,Cepeda C,Li Y,Dong H,Levine MS,Yang XW

    更新日期:2014-05-01 00:00:00

  • Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease.

    abstract::Neurovascular dysfunction substantially contributes to Alzheimer disease. Here, we show that transcriptional profiling of human brain endothelial cells (BECs) defines a subset of genes whose expression is age-independent but is considerably altered in Alzheimer disease, including the homeobox gene MEOX2 (also known as...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1287

    authors: Wu Z,Guo H,Chow N,Sallstrom J,Bell RD,Deane R,Brooks AI,Kanagala S,Rubio A,Sagare A,Liu D,Li F,Armstrong D,Gasiewicz T,Zidovetzki R,Song X,Hofman F,Zlokovic BV

    更新日期:2005-09-01 00:00:00

  • A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis.

    abstract::Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAE...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0523-2

    authors: Johnson DB,McDonnell WJ,Gonzalez-Ericsson PI,Al-Rohil RN,Mobley BC,Salem JE,Wang DY,Sanchez V,Wang Y,Chastain CA,Barker K,Liang Y,Warren S,Beechem JM,Menzies AM,Tio M,Long GV,Cohen JV,Guidon AC,O'Hare M,Chandra S

    更新日期:2019-08-01 00:00:00

  • Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab.

    abstract::Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung canc...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0134-3

    authors: Gandara DR,Paul SM,Kowanetz M,Schleifman E,Zou W,Li Y,Rittmeyer A,Fehrenbacher L,Otto G,Malboeuf C,Lieber DS,Lipson D,Silterra J,Amler L,Riehl T,Cummings CA,Hegde PS,Sandler A,Ballinger M,Fabrizio D,Mok T,Shames

    更新日期:2018-09-01 00:00:00

  • Autocrine angiogenic vascular prosthesis with bone marrow transplantation.

    abstract::Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permane...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0196-90

    authors: Noishiki Y,Tomizawa Y,Yamane Y,Matsumoto A

    更新日期:1996-01-01 00:00:00

  • Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

    abstract::Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites1. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor rea...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0266-5

    authors: Scheper W,Kelderman S,Fanchi LF,Linnemann C,Bendle G,de Rooij MAJ,Hirt C,Mezzadra R,Slagter M,Dijkstra K,Kluin RJC,Snaebjornsson P,Milne K,Nelson BH,Zijlmans H,Kenter G,Voest EE,Haanen JBAG,Schumacher TN

    更新日期:2019-01-01 00:00:00

  • A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

    abstract::The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2063

    authors: Barlow JL,Drynan LF,Hewett DR,Holmes LR,Lorenzo-Abalde S,Lane AL,Jolin HE,Pannell R,Middleton AJ,Wong SH,Warren AJ,Wainscoat JS,Boultwood J,McKenzie AN

    更新日期:2010-01-01 00:00:00

  • Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria.

    abstract::The role of nitric oxide (NO) in the genesis of cerebral malaria is controversial. Most investigators propose that the unfortunate consequence of the high concentrations of NO produced to kill the parasite is the development of cerebral malaria. Here we have tested this high NO bioavailability hypothesis in the settin...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1499

    authors: Gramaglia I,Sobolewski P,Meays D,Contreras R,Nolan JP,Frangos JA,Intaglietta M,van der Heyde HC

    更新日期:2006-12-01 00:00:00

  • In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides.

    abstract::A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0398-285

    authors: Kren BT,Bandyopadhyay P,Steer CJ

    更新日期:1998-03-01 00:00:00

  • Oral immunization with an anti-idiotypic antibody to the exoglycolipid antigen protects against experimental Chlamydia trachomatis infection.

    abstract::Chlamydia trachomatis is the leading cause worldwide of preventable infectious blindness (trachoma) and sexually transmitted disease, including nongonoccocal urethritis and pelvic inflammatory disease. To date, no effective vaccine against C. trachomatis infection has been identified. A monoclonal anti-idiotypic antib...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1096-1116

    authors: Whittum-Hudson JA,An LL,Saltzman WM,Prendergast RA,MacDonald AB

    更新日期:1996-10-01 00:00:00

  • Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.

    abstract::Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to ident...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3560

    authors: Qin H,Lerman B,Sakamaki I,Wei G,Cha SC,Rao SS,Qian J,Hailemichael Y,Nurieva R,Dwyer KC,Roth J,Yi Q,Overwijk WW,Kwak LW

    更新日期:2014-06-01 00:00:00

  • Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy.

    abstract::We show that the fraction of proliferating CD4+ lymphocytes is similar in HIV-infected subjects in the early stage of disease and in HIV-negative subjects, whereas the fraction of proliferating CD8+ lymphocytes is increased 6.8-fold in HIV-infected subjects. After initiation of antiviral therapy, there is a late incre...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0798-794

    authors: Fleury S,de Boer RJ,Rizzardi GP,Wolthers KC,Otto SA,Welbon CC,Graziosi C,Knabenhans C,Soudeyns H,Bart PA,Gallant S,Corpataux JM,Gillet M,Meylan P,Schnyder P,Meuwly JY,Spreen W,Glauser MP,Miedema F,Pantaleo G

    更新日期:1998-07-01 00:00:00

  • Wearable sensor data and self-reported symptoms for COVID-19 detection.

    abstract::Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-020-1123-x

    authors: Quer G,Radin JM,Gadaleta M,Baca-Motes K,Ariniello L,Ramos E,Kheterpal V,Topol EJ,Steinhubl SR

    更新日期:2021-01-01 00:00:00

  • Fighting tobacco dependence in Europe.

    abstract::The World Health Organization estimates that tobacco will become the largest single health problem by 2020, causing an estimated 8.4 million deaths annually. But the smoking burden will not be distributed evenly across the globe; deaths in developed nations are set to rise 50% to 2.4 million while those in Asia will s...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/83281

    authors: Raw M

    更新日期:2001-01-01 00:00:00

  • Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.

    abstract::Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to thera...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4407

    authors: Romero R,Sayin VI,Davidson SM,Bauer MR,Singh SX,LeBoeuf SE,Karakousi TR,Ellis DC,Bhutkar A,Sánchez-Rivera FJ,Subbaraj L,Martinez B,Bronson RT,Prigge JR,Schmidt EE,Thomas CJ,Goparaju C,Davies A,Dolgalev I,Heguy A,A

    更新日期:2017-11-01 00:00:00

  • Getting biological about the genetics of diabetes.

    abstract::New technology has provided methods for collecting large amounts of data reflecting gene expression, metabolite and protein abundance, and post-translational modification of proteins. Integration of these various data sets enable the genetic mapping of many new phenotypes and facilitates the creation of network models...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0410-388

    authors: Newgard CB,Attie AD

    更新日期:2010-04-01 00:00:00

  • Sema3a maintains normal heart rhythm through sympathetic innervation patterning.

    abstract::Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a,...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1570

    authors: Ieda M,Kanazawa H,Kimura K,Hattori F,Ieda Y,Taniguchi M,Lee JK,Matsumura K,Tomita Y,Miyoshi S,Shimoda K,Makino S,Sano M,Kodama I,Ogawa S,Fukuda K

    更新日期:2007-05-01 00:00:00

  • The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

    abstract::The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3974

    authors: Miner JJ,Daniels BP,Shrestha B,Proenca-Modena JL,Lew ED,Lazear HM,Gorman MJ,Lemke G,Klein RS,Diamond MS

    更新日期:2015-12-01 00:00:00

  • Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.

    abstract::Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0339-5

    authors: Schalper KA,Rodriguez-Ruiz ME,Diez-Valle R,López-Janeiro A,Porciuncula A,Idoate MA,Inogés S,de Andrea C,López-Diaz de Cerio A,Tejada S,Berraondo P,Villarroel-Espindola F,Choi J,Gúrpide A,Giraldez M,Goicoechea I,Gallego Pe

    更新日期:2019-03-01 00:00:00

  • In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria.

    abstract::The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3929

    authors: Geva-Zatorsky N,Alvarez D,Hudak JE,Reading NC,Erturk-Hasdemir D,Dasgupta S,von Andrian UH,Kasper DL

    更新日期:2015-09-01 00:00:00

  • Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1.

    abstract::How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Stro...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1297-1389

    authors: Gauduin MC,Parren PW,Weir R,Barbas CF,Burton DR,Koup RA

    更新日期:1997-12-01 00:00:00

  • PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.

    abstract::Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm977

    authors: Göggel R,Winoto-Morbach S,Vielhaber G,Imai Y,Lindner K,Brade L,Brade H,Ehlers S,Slutsky AS,Schütze S,Gulbins E,Uhlig S

    更新日期:2004-02-01 00:00:00