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1.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34782469

RESUMEN

Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Fosfatasas de Especificidad Dual/genética , Predisposición Genética a la Enfermedad/genética , Mutación de Línea Germinal , Animales , Enfermedades Autoinmunes/genética , Femenino , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Islotes Pancreáticos/metabolismo , Complejo Mayor de Histocompatibilidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Fosfatasas de la Proteína Quinasa Activada por Mitógenos , Mutación
2.
Allergy ; 75(1): 104-115, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31321780

RESUMEN

BACKGROUND: The hygiene hypothesis proposes that reduced exposure to infectious agents in early life would explain the increase of allergic and autoimmune diseases observed over the past decades in high-income countries. METHODS: We conducted a matched case-control study on incident atopic dermatitis (AD). Cases were 426 outpatient children with a first diagnosis of incident AD. Controls were 426 children attending a pediatric/dermatological visit for nonatopic disorders matched to cases (1:1). Particular attention was paid to the time elapsed between the markers of microbial exposure and disease onset, and we considered for controls the same time window of exposures from birth as his/her matched case. Odds ratios (ORs) were computed using multivariable conditional logistic regression models, according to center, sex, age, and period of enrollment, and including as potential confounders a family history of any allergy in parents, type of delivery, having siblings, keeping pets, age at weaning, and having had ≥4 infections. RESULTS: The OR of AD first occurrence was 0.35 (P-value = .039) for children who had experienced ≥4 infections compared with those with no infections. A decreasing trend in risk was observed with increasing number of siblings (P-value = .023), the protective effect reaching about 40% for children with 2 or more siblings (OR = 0.62; P-value = .048). Pet keeping, in particular daily contact with dogs, was inversely associated with AD risk (OR = 0.40; P-value = .004). CONCLUSIONS: These results support the hygiene hypothesis in its broad sense. Early-life environmental exposures, including pathogens and commensals, act as "microbes contact carriers" influencing immune system balance early in life.


Asunto(s)
Dermatitis Atópica/epidemiología , Hipótesis de la Higiene , Infecciones/epidemiología , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Incidencia , Lactante , Italia/epidemiología , Masculino , Oportunidad Relativa
3.
An Acad Bras Cienc ; 91(suppl 3): e20190339, 2019 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-31460595

RESUMEN

Genetic drift is the fortuitous occurrence of genetic events that when they become fixed modify the genome of populations. They can take the form of mutations of single nucleotides (SNPs), the insertion or deletion of short sequences (Indels) or the repetitions of short sequences (CNV i.e. copy number variants) or long insertions or deletion (structural modifications). Their frequency is 10-9 to 10-8 depending on the species, or 50 to 100 per birth in humans. The incidence of these de novo mutations is higher when the father is old at conception. It thus appears that genetic drift, which constitutes the initial element of evolution, has a very strong dynamics. Its intervention in the appearance or disappearance of some major phenotypes is complicated by the uncertainties about the genetic mechanisms in heritability which, paradoxically, are only partially understood.


Asunto(s)
Evolución Molecular , Flujo Genético , Mutación INDEL/genética , Mamíferos/genética , Animales , Humanos , Ratones , Ratas
4.
Semin Immunol ; 23(3): 174-81, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21846589

RESUMEN

Type 1 diabetes is an autoimmune disease. It was thus logical to attempt preventing or stopping the progression of the disease by immunotherapy. Following the strategies used in organ transplantation, the first trials in the 80s used cyclosporin in patients presenting recently diagnosed Type 1 diabetes. The effect was spectacular but waned when the treatment was stopped as the effect was non antigen-specific. Going back from bed to bench-side major efforts were then devoted to device strategies allowing induction or restoration of self-tolerance. Two major approaches provided encouraging results when used in spontaneous models of autoimmune diabetes that are the use of ß-cell autoantigens and of monoclonal antibodies to CD3. Based on these results academic phase II trials and subsequently pharmaceutically driven phase III trials were launched. Results are now available and when critically analyzed in the frame of these last three decades they provide support to the possibility of making step by step immunotherapy available to all new onset diabetic patients with a hope of inducing long-term remission of the disease if the treatment is started sufficiently early, immediately after diagnosis.


Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Inmunoterapia , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Autoantígenos/inmunología , Complejo CD3/inmunología , Ciclosporina/uso terapéutico , Diabetes Mellitus Tipo 1/historia , Diabetes Mellitus Tipo 1/inmunología , Historia del Siglo XX , Humanos , Inmunoterapia/historia , Células Secretoras de Insulina/inmunología , Autotolerancia/inmunología
5.
Nat Rev Immunol ; 3(3): 189-98, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12658267

RESUMEN

Having been long debated, the notion of suppressor T cells--renamed regulatory T cells--is back on the map, but many questions remain regarding the nature of these regulatory cells. Are they specialized cells? What are their phenotype, antigen specificity, mode of action and, above all, biological (and immunopathological) relevance? The predominant role of naturally occurring CD4+CD25+ T cells has been emphasized recently. Other cell types, however, contribute to immunoregulation also, whether they arise spontaneously during ontogeny or during the course of an adaptive immune response.


Asunto(s)
Subgrupos Linfocitarios/inmunología , Linfocitos T Reguladores/inmunología , Animales , Antígenos CD4/inmunología , Citocinas/inmunología , Humanos , Tolerancia Inmunológica , Inmunidad Innata , Receptores de Interleucina-2/inmunología , Especificidad de la Especie
6.
An Acad Bras Cienc ; 91(suppl 3): e20191040, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31576936
7.
J Allergy Clin Immunol ; 132(3): 616-622.e7, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23711545

RESUMEN

BACKGROUND: Findings on pet exposure and the risk of atopic dermatitis (AD) in children are inconsistent. OBJECTIVE: With the aim to summarize the results of exposure to different pets on AD, we undertook a meta-analysis of epidemiologic studies on this issue. METHODS: In August 2012, we conducted a systematic literature search in Medline and Embase. We included analytic studies considering exposure to dogs, cats, other pets, or pets overall during pregnancy, infancy, and/or childhood, with AD assessment performed during infancy or childhood. We calculated summary relative risks and 95% CIs using both fixed- and random-effects models. We computed summary estimates across selected subgroups. RESULTS: Twenty-six publications from 21 birth cohort studies were used in the meta-analyses. The pooled relative risks of AD for exposure versus no exposure were 0.72 (95% CI, 0.61-0.85; I(2) = 46%; results based on 15 studies) for exposure to dogs, 0.94 (95% CI, 0.76-1.16; I(2) = 54%; results based on 13 studies) for exposure to cats, and 0.75 (95% CI, 0.67-0.85; I(2) = 54%; results based on 11 studies) for exposure to pets overall. No heterogeneity emerged across the subgroups examined, except for geographic area. CONCLUSION: This meta-analysis reported a favorable effect of exposure to dogs and pets on the risk of AD in infants or children, whereas no association emerged with exposure to cats.


Asunto(s)
Gatos/inmunología , Dermatitis Atópica/epidemiología , Perros/inmunología , Mascotas/inmunología , Animales , Estudios de Cohortes , Exposición a Riesgos Ambientales , Humanos , Riesgo
8.
C R Biol ; 346(S2): 91-93, 2024 03 29.
Artículo en Francés | MEDLINE | ID: mdl-38275107

RESUMEN

François Gros was Permanent Secretary of the French Academy of Sciences from 1991 to 2000. His immense scientific knowledge, his tireless efforts to develop international relations, particularly with developing countries, and his exceptional personality have greatly contributed to the modernisation and influence of the Academy.


François Gros a été secrétaire perpétuel de l'Académie des sciences de 1991 à 2000. Son immense culture scientifique, son activité incessante pour le développement des relations internationales en particulier vers les pays en développement, et sa personnalité exceptionnelle ont grandement contribué à la modernisation et au rayonnement de l'Académie.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39284671

RESUMEN

In November 2022, teplizumab became the first drug approved to delay the course of any autoimmune disease and to change the course of type 1 diabetes (T1D) since the discovery of insulin. The path to its approval took more than 30 years with both successes and failures along the way that would have normally led to its abandonment in other circumstances. Development of the drug was based on studies in preclinical models and parallels efforts in transplantation. From a series of innovative adaptations in response to issues related to adverse events and immunogenicity, humanized Fc receptors (FcR) nonbinding antibodies were developed with improved clinical outcomes and safety as well as new mechanisms. Importantly, as a result of these developments, teplizumab has been able to achieve efficacy over extended periods of time without global immune suppression. The approval of teplizumab represents a significant first step toward achieving escape from T1D and, in the future, reversal of the disease.

10.
Nat Genet ; 36(8): 837-41, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15247916

RESUMEN

Previous studies have suggested more than 20 genetic intervals that are associated with susceptibility to type 1 diabetes (T1D), but identification of specific genes has been challenging and largely limited to known candidate genes. Here, we report evidence for an association between T1D and multiple single-nucleotide polymorphisms in 197 kb of genomic DNA in the IDDM5 interval. We cloned a new gene (SUMO4), encoding small ubiquitin-like modifier 4 protein, in the interval. A substitution (M55V) at an evolutionarily conserved residue of the crucial CUE domain of SUMO4 was strongly associated with T1D (P = 1.9 x 10(-7)). SUMO4 conjugates to I kappa B alpha and negatively regulates NF kappa B transcriptional activity. The M55V substitution resulted in 5.5 times greater NF kappa B transcriptional activity and approximately 2 times greater expression of IL12B, an NF kappa B-dependent gene. These findings suggest a new pathway that may be implicated in the pathogenesis of T1D.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/fisiología , Secuencia de Aminoácidos , Estudios de Casos y Controles , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Datos de Secuencia Molecular , Mapeo Físico de Cromosoma , Polimorfismo de Nucleótido Simple , Homología de Secuencia de Aminoácido
11.
Epidemiology ; 23(3): 402-14, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22441545

RESUMEN

BACKGROUND: The study of probiotics to prevent allergic conditions has yielded conflicting results in children. We undertook a meta-analysis of randomized controlled trials to investigate whether probiotic use during pregnancy and early life decreases the incidence of atopic dermatitis and immunoglobulin E (IgE)-associated atopic dermatitis in infants and young children. METHODS: We performed a systematic literature search in Medline, Embase, and Cochrane Library, updated to October 2011. The intervention was diet supplementation with probiotics versus placebo. Primary outcomes were incidence of atopic dermatitis and IgE-associated atopic dermatitis. We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs), using both fixed- and random-effects models. We computed summary estimates across several strata, including study period, type of patient, dose, and duration of intervention, and we assessed the risk of bias within and across trials. RESULTS: We identified 18 publications based on 14 studies. Meta-analysis demonstrated that probiotic use decreased the incidence of atopic dermatitis (RR = 0.79 [95% CI = 0.71-0.88]). Studies were fairly homogeneous (I = 24.0%). The corresponding RR of IgE-associated atopic dermatitis was 0.80 (95% CI = 0.66-0.96). No appreciable difference emerged across strata, nor was there evidence of publication bias. CONCLUSIONS: This meta-analysis provided evidence in support of a moderate role of probiotics in the prevention of atopic dermatitis and IgE-associated atopic dermatitis in infants. The favorable effect was similar regardless of the time of probiotic use (pregnancy or early life) or the subject(s) receiving probiotics (mother, child, or both).


Asunto(s)
Dermatitis Atópica/prevención & control , Probióticos/uso terapéutico , Dermatitis Atópica/inmunología , Femenino , Humanos , Hipótesis de la Higiene , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Modelos Estadísticos , Embarazo , Atención Prenatal , Resultado del Tratamiento
12.
Blood ; 115(6): 1145-55, 2010 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-20007541

RESUMEN

Here we report a unique situation in which an early and synchronized Epstein-Barr virus (EBV) reactivation was induced by a 6-day course of treatment with a humanized CD3-specific monoclonal antibody in patients with recent onset of type 1 diabetes. The virologic and immunologic analysis demonstrated that this reactivation was transient, self-limited, and isolated, associated with the rapid advent of an EBV-specific T-cell response. The anti-CD3 antibody administration induced short-lasting immunosuppression and minor yet clear-cut signs of T-cell activation that preceded viral reactivation. Early posttransplant monitoring of renal and islet allograft recipients showed that no comparable phenomenon was observed after the administration of full-dose immunosuppressive therapy. This EBV reactivation remains of no apparent clinical concern over the long term and should not preclude further development of therapeutic anti-CD3 antibodies. This phenomenon may also direct new research avenues to understand the still ill-defined nature of stimuli triggering EBV reactivation in vivo.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Complejo CD3/inmunología , Infecciones por Virus de Epstein-Barr/terapia , Supervivencia de Injerto/inmunología , Herpesvirus Humano 4/fisiología , Linfocitos B/inmunología , ADN Viral/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/virología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Citometría de Flujo , Humanos , Trasplante de Riñón , Tonsila Palatina/citología , Fenotipo , Placebos , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunología , Carga Viral , Activación Viral
13.
Dis Model Mech ; 15(6)2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35502705

RESUMEN

Genetic association studies of type 1 diabetes (T1D) in humans, and in congenic non-obese diabetic (NOD) mice harboring DNA segments from T1D-resistant mice, face the challenge of assigning causation to specific gene variants among many within loci that affect disease risk. Here, we created random germline mutations in NOD/NckH mice and used automated meiotic mapping to identify mutations modifying T1D incidence and age of onset. In contrast with association studies in humans or congenic NOD mice, we analyzed a relatively small number of genetic changes in each pedigree, permitting implication of specific mutations as causative. Among 844 mice from 14 pedigrees bearing 594 coding/splicing changes, we identified seven mutations that accelerated T1D development, and five that delayed or suppressed T1D. Eleven mutations affected genes not previously known to influence T1D (Xpnpep1, Herc1, Srrm2, Rapgef1, Ppl, Zfp583, Aldh1l1, Col6a1, Ccdc13, Cd200r1, Atrnl1). A suppressor mutation in Coro1a validated the screen. Mutagenesis coupled with automated meiotic mapping can detect genes in which allelic variation influences T1D susceptibility in NOD mice. Variation of some of the orthologous/paralogous genes may influence T1D susceptibility in humans.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animales , Diabetes Mellitus Tipo 1/genética , Etilnitrosourea , Predisposición Genética a la Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Mutación/genética , Ubiquitina-Proteína Ligasas/genética
14.
Nat Med ; 9(9): 1202-8, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12937416

RESUMEN

CD3-specific antibodies have the unique capacity to restore self-tolerance in established autoimmunity. They induce long-term remission of overt diabetes in nonobese diabetic (NOD) mice and in human type I diabetes. The underlying mechanisms had been unclear until now. Here we report that treatment with CD3epsilon-specific antibodies induces transferable T-cell-mediated tolerance involving CD4+CD25+ cells. However, these CD4+CD25+ T cells are distinct from naturally occurring regulatory T cells that control physiological autoreactivity. CD3-specific antibody treatment induced remission in NOD Cd28-/- mice that were devoid of such regulatory cells. Remission of diabetes was abrogated by coadministration of a neutralizing transforming growth factor (TGF)-beta-specific antibody. The central role of TGF-beta was further suggested by its increased, long-lasting production by CD4+ T cells from tolerant mice. These data explain the intriguing tolerogenic effect of CD3-specific antibodies and position them as the first clinically applicable pharmacological stimulant of TGF-beta-producing regulatory CD4+ T cells.


Asunto(s)
Complejo CD3/inmunología , Diabetes Mellitus Tipo 1/inmunología , Tolerancia Inmunológica/inmunología , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Anticuerpos/farmacología , Antígenos CD , Antígenos de Diferenciación/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígeno CTLA-4 , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Tolerancia Inmunológica/efectos de los fármacos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Receptores de Interleucina-2/inmunología , Receptores de Interleucina-2/metabolismo , Bazo/citología , Bazo/inmunología , Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta/inmunología
15.
Bull Acad Natl Med ; 195(6): 1223-33, 2011 Jun.
Artículo en Francés | MEDLINE | ID: mdl-22530516

RESUMEN

Quantitative analysis of publications and their citations, a procedure known as bibliometrics, has become increasingly important in the evaluation of scientists and clinicians. In the clinical setting, bibliometrics is used for the calculation of hospital budgets. While bibliometrics is attractive because it rapidly provides numbers that bear a certain relation to scientific productivity, it is often misused. The parameters chosen are questionable and sometimes worthless because of material errors or inappropriate use. More importantly, reducing the activity of a scientist or physician simply to the number of his or her publications or citations, without analyzing the importance and impact of the work itself can lead to serious errors.


Asunto(s)
Bibliometría , Médicos , Investigación , Estudios de Evaluación como Asunto , Guías como Asunto
16.
C R Biol ; 344(1): 7-18, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34213845

RESUMEN

Immunity to the SARS-CoV-2 virus ensures protection against reinfection by this virus thanks to the combined action of neutralizing antibodies and T lymphocytes specific to viral proteins, in particular the Spike protein. It must be distinguished from the immune response that ensures healing of the infection following contamination that involves innate immunity, particularly type 1 interferons, and which is followed by adaptive cellular and humoral immunity. The importance of the effect of interferons is highlighted by the occurrence of severe forms of the disease in genetically deficient subjects or in patients with antibodies neutralizing type 1 interferon. Herd immunity is not an individual biological property. It is a mathematical property that qualifies the fact that when the proportion of subjects with individual immunity is high enough, there is little chance that an epidemic can occur. The level of that proportion-the herd immunity of the population can be computed under theoretical, often unrealistic, hypotheses, and is difficult to assess in natural conditions.


L'immunité individuelle contre le virus SARS-CoV-2 assure la protection contre la réinfection par ce virus grâce à l'action conjuguée des anticorps neutralisants et des lymphocytes T spécifiques des protéines virales, notamment la protéine Spike (spicule). Il faut la distinguer de la réponse immunitaire qui assure la guérison de l'infection dans les jours suivant la contamination. Celle-ci fait intervenir l'immunité innée et tout particulièrement les interférons de type 1 puis l'immunité adaptative cellulaire et humorale. L'importance de l'effet des interférons est soulignée par la survenue de formes graves chez des sujets génétiquement déficients dans leur synthèse ou encore des patients présentant des anticorps neutralisant l'interféron de type 1. L'immunité collective caractérise la faible probabilité de développement d'une épidémie dans une population ayant un pourcentage élevé de sujets présentant une immunité individuelle. Le taux d'immunité collective nécessaire pour faire disparaître l'épidémie a été calculé dans des modèles mathématiques supposant la panmixie ; il est difficile à évaluer dans les populations réelles.


Asunto(s)
COVID-19 , Inmunidad Colectiva , Anticuerpos Neutralizantes , Humanos , SARS-CoV-2
19.
Front Immunol ; 11: 615192, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33584703

RESUMEN

Initially described for allergic diseases, the hygiene hypothesis was extended to autoimmune diseases in the early 2000s. A historical overview allows appreciation of the development of this concept over the last two decades and its discussion in the context of evolution. While the epidemiological data are convergent, with a few exceptions, the underlying mechanisms are multiple and complex. A major question is to determine what is the respective role of pathogens, bacteria, viruses, and parasites, versus commensals. The role of the intestinal microbiota has elicited much interest, but is it a cause or a consequence of autoimmune-mediated inflammation? Our hypothesis is that both pathogens and commensals intervene. Another question is to dissect what are the underlying cellular and molecular mechanisms. The role of immunoregulatory cytokines, in particular interleukin-10 and TGF beta is probably essential. An important place should also be given to ligands of innate immunity receptors present in bacteria, viruses or parasites acting independently of their immunogenicity. The role of Toll-Like Receptor (TLR) ligands is well documented including via TLR ligand desensitization.


Asunto(s)
Autoinmunidad , Hipótesis de la Higiene , Simbiosis , Animales , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/prevención & control , Bacterias/inmunología , Evolución Biológica , Causalidad , Niño , Citocinas/fisiología , Modelos Animales de Enfermedad , Disbiosis/complicaciones , Exposición a Riesgos Ambientales , Métodos Epidemiológicos , Microbioma Gastrointestinal/inmunología , Interacciones Huésped-Patógeno/inmunología , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Hipersensibilidad/prevención & control , Inmunidad Innata , Hombre de Neandertal/genética , Hombre de Neandertal/inmunología , Parásitos/inmunología , Procesos Estocásticos , Receptores Toll-Like/fisiología , Virus/inmunología
20.
J Clin Invest ; 116(9): 2325-7, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16955134

RESUMEN

It is now well established that a distinct subset of T lymphocytes is essential for downregulating immune responses to both endogenous (self) and exogenous antigens. These Tregs are CD4+ and express high levels of CD25 (the alpha chain of the IL-2 receptor) and the transcription factor Foxp3. The mechanisms determining the lifespan, homeostasis, and in vivo generation of these Tregs are still ill defined. A study by Vukmanovic-Stejic et al. in this issue of the JCI shows that in humans, Tregs are present throughout life but that despite their high throughput, they are short lived (see the related article beginning on page 2423). It is thus unlikely that all CD4+ CD25hi Foxp3+ Tregs are generated as a separate lineage in the thymus. The authors propose that during adulthood, Tregs essentially emerge at the periphery from the memory T cell pool.


Asunto(s)
Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Antígenos CD/inmunología , Humanos , Inmunidad Celular , Inmunidad Innata
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