RESUMEN
Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (ß=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.
Asunto(s)
Cognición , Glaucoma , Anciano , Brasil , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Pruebas Neuropsicológicas , AutoinformeRESUMEN
Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Glaucoma , Cognición , Brasil , Estudios Transversales , Estudios Longitudinales , Autoinforme , Pruebas NeuropsicológicasRESUMEN
Resumo O artigo explora as possibilidades e os limites das noções de 'fundamentalismo', tolerância' e 'intolerância' e avalia os potenciais ganhos das noções de 'hostilidade' e 'hospitalidade' para a análise de controvérsias contemporâneas sobre política sexual. Elabora sobre uma controvérsia que se instaurou em torno da consulta popular sobre o casamento entre pessoas do mesmo sexo na Irlanda, em 2015. Procura-se delinear os contornos das duas noções propostas como categorias teóricas em antropologia. O artigo discute conceitos do campo da antropologia da religião a partir da análise de controvérsias e da análise qualitativa de um caso, com base em pesquisa documental e bibliográfica.
Abstract This article explores the possibilities and limits of the notions of 'fundamentalism', 'tolerance', and intolerance', and assesses the potential gains brought by the notions of 'hostility' and 'hospitality' to the analysis of controversies about sexual politics. It elaborates on a controversy around the referendum on same-sex marriage in Ireland, in 2015. The discussion seeks to delineate the contours of the latter two notions as theoretical categories in Anthropology. The article consists of a theoretical discussion in the Anthropology of Religion, focused on controversies and the qualitative analysis of one case, based on documentary and bibliographical research.
Resumen El artículo explora las posibilidades y límites de las nociones de 'fundamentalismo', 'tolerancia' e 'intolerancia' y evalúa los beneficios potenciales que aportan las nociones de 'hostilidad' y 'hospitalidad' para el análisis de controversias contemporáneas sobre política sexual. Elabora sobre una controversia que se instauró en torno a la consulta popular sobre el matrimonio entre personas del mismo sexo en Irlanda en 2015. La discusión plantea los contornos de las dos nociones propuestas como categorías teóricas en antropología. El artículo consiste en una en discusión conceptual de la antropología de la religión, a partir del análisis de controversias y el análisis cualitativo de un caso, con base en investigación documental y bibliográfica.
Asunto(s)
Humanos , Homosexualidad , Sexualidad , Hostilidad , Derechos Humanos , Tolerancia , Religión , Matrimonio , Catolicismo , IrlandaAsunto(s)
Envejecimiento , Síndromes de Inmunodeficiencia , Estado Nutricional , Osteoporosis , Sarcopenia , Anciano , Animales , Huesos/patología , Humanos , Sistema Inmunológico/patología , Síndromes de Inmunodeficiencia/dietoterapia , Músculo Esquelético/patología , Osteoporosis/dietoterapia , Sarcopenia/dietoterapiaRESUMEN
OBJECTIVE: This study investigates the association between MNA results and frailty status in community-dwelling older adults. In addition the relevance of singular MNA items and subscores in this regard was tested. DESIGN: Cross-sectional study. SETTING: Community-dwelling older adults were recruited in the region of Nürnberg, Germany. PARTICIPANTS: 206 volunteers aged 75 years or older without cognitive impairment (Mini Mental State Examination >24 points), 66.0% female. MEASUREMENTS: Frailty was defined according to Fried et al. as presence of three, pre-frailty as presence of one or two of the following criteria: weight loss, exhaustion, low physical activity, low handgrip strength and slow walking speed. Malnutrition (<17 points) and the risk of malnutrition (17-23.5 points) were determined by MNA®. RESULTS: 15.1% of the participants were at risk of malnutrition, no participant was malnourished. 15.5 % were frail, 39.8% pre-frail and 44.7% non-frail. 46.9% of the frail, 12.2% of the pre-frail and 2.2% of the non-frail participants were at risk of malnutrition (p<0.001). Hence, 90% of those at risk of malnutrition were either pre-frail or frail. For the anthropometric, dietary, subjective and functional, but not for the general MNA subscore, frail participants scored significantly lower than pre-frail (p<0.01), and non-frail participants (p<0.01). Twelve of the 18 MNA items were also significantly associated with frailty (p<0.05). CONCLUSIONS: These results underline the close association between frailty syndrome and nutritional status in older persons. A profound understanding of the interdependency of these two geriatric concepts will represent the basis for successful treatment strategies.
Asunto(s)
Anciano Frágil , Desnutrición/diagnóstico , Desnutrición/epidemiología , Evaluación Nutricional , Estado Nutricional , Anciano , Anciano de 80 o más Años , Estudios Transversales , Dieta , Fatiga , Femenino , Evaluación Geriátrica/métodos , Alemania , Fuerza de la Mano , Humanos , Masculino , Prevalencia , Encuestas y Cuestionarios , Pérdida de PesoRESUMEN
BACKGROUND: Frailty is a widespread geriatric syndrome, but its relationship with body composition is largely unknown. OBJECTIVES: Assess the relationship between body composition and frailty in older persons. DESIGN, PARTICIPANTS AND SETTING: Cross-sectional data analyses in 120 community-dwelling older persons (50 men, 70 women, mean age 78.5 ± 6 yr). MEASUREMENTS: Frailty was measured according to Fried's criteria and calculated as a score, and also a binary variable. Anthropometric measures were obtained (height, weight), and body composition (total lean body mass, appendicular skeletal muscle mass (ASM), total fat mass, and percentage fat), assessed by dual energy x-ray absorptiometry. Multiple regression and logistic regression analyses stratified by gender were conducted. RESULTS: Frailty, as a binary measure, was more prevalent in women than men (67.1% vs 46% p=0.04). Prevalence of low muscle mass (ASM/ht2) was higher in men than in women (40.0% vs 32.9%, p=0.04). Using gender-specific percentage fat cut-scores (27% men, 38% women, respectively) obesity was more prevalent in women than men (58.6% vs 34%, respectively, p=0.01). Multiple regression models showed age as an independent associated factor of frailty in men (ß 0.310, p=0.009) and women (ß .581 p<0.001). ASM/ht2 was a significant associated factor in men (ß -0.517, p<0.001) and trended towards significance in women (ß -0.188, p=0.06). Percentage fat was a significant associated factor in women only (ß 0.234, p=0.02). Logistic regression with frailty as a binary dependent variable yielded similar results. CONCLUSION: In this sample of older adults, the significant associated factor of frailty in men was ASM/ht2, whereas it was percentage fat in women. These associations were independent of age. With increasing longevity and the high prevalence of sarcopenia and obesity in older populations, these findings have public health implications. Larger sample and specifically designed studies are needed in order to confirm and extend these findings.
RESUMEN
Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.
Asunto(s)
Proteínas de Fase Aguda , Inmunidad Mucosa , Recién Nacido/inmunología , Receptores de Lipopolisacáridos/inmunología , Glicoproteínas de Membrana , Leche Humana/inmunología , Proteínas Portadoras , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Células HT29 , Humanos , Interleucina-8/biosíntesis , Mucosa Intestinal/inmunología , Receptores de Lipopolisacáridos/aislamiento & purificación , Lipopolisacáridos/inmunología , Células Tumorales CultivadasRESUMEN
The nature of peptide binding to MHC molecules is intrinsically degenerate, in what, one given MHC molecule can accommodate numerous peptides which are structurally diverse, and one given peptide can bind to different alleles. The structure of the MHC class II molecules allows peptides to extend out of the binding groove at both ends and these residues can potentially influence the stability and persistence of peptide/class II complexes. We have previously shown that both I-E(k) and I-A(k)-restricted T cell hybridomas could be generated against the Hb(64-76) epitope. In this study, we characterized the binding register of the Hb(64-76) epitope to I-A(k), and showed that it was shifted by one residue in comparison to its binding to I-E(k), and did not use a dominant anchor residue at P1. This conclusion was further supported by the modeling of the Hb(64-76) epitope bound to I-A(k), which revealed that all of its putative anchor residues fit into their corresponding pockets. We identified the naturally processed Hb epitopes presented by both I-E(k) and I-A(k), and found that they consisted of different species. Those associated with I-A(k) being 20-22 residues long, whereas, those found to I-E(k) contained 14-16 residues. These findings suggested that the lack of a dominant P1 anchor could be compensated by the selection of longer peptides. Overall, these studies revealed the Hb(64-76) epitope bound to I-E(k) and I-A(k) in distinct registers and lengths, demonstrating the plasticity MHC molecules have in generating distinct TCR ligands from the same amino acid sequence.
Asunto(s)
Presentación de Antígeno , Hemoglobinas/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Fragmentos de Péptidos/inmunología , Sitios de Unión , Unión Competitiva , Epítopos , Hemoglobinas/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Modelos Moleculares , Fragmentos de Péptidos/metabolismo , Péptidos/química , Unión ProteicaRESUMEN
Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.
Asunto(s)
Bacterias/inmunología , Receptores de Lipopolisacáridos/metabolismo , Leche Humana/inmunología , Leche Humana/microbiología , Secuencia de Aminoácidos , Animales , Bovinos , Calostro/inmunología , Femenino , Humanos , Inmunidad Innata , Inmunidad Mucosa , Alimentos Infantiles/análisis , Recién Nacido , Intestinos/inmunología , Intestinos/microbiología , Receptores de Lipopolisacáridos/sangre , Receptores de Lipopolisacáridos/genética , Datos de Secuencia Molecular , Embarazo , SolubilidadRESUMEN
Human breast milk is rich in nutrients, hormones, growth factors and immunoactive molecules, which influence the growth, development and immune status of the newborn infant. Although several of these factors are also present in bovine milk, the greater susceptibility of the formula-fed infant to infection and disease and the development of allergy is often attributed to the reduced level of protective factors in milk formulas. Nevertheless, modifying manufacturing processes may preserve the biological activity of some bioactive molecules in end products. Transforming growth factor (TGF)-beta is one such molecule. TGF-beta is a polypeptide, which has been described in both human and bovine milk. It is implicated in many processes, including epithelial cell growth and differentiation, development, carcinogenesis and immune regulation. The present article discusses the biological activity of TGF-beta2 that has been preserved and activated in a cow's milk-based product. More specifically, it addresses possible mechanisms of action in the intestinal lumen and speculates on how milk products containing naturally occurring TGF-beta2 could be exploited in functional foods for the infant or as therapies for specific intestinal diseases.
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Leche Humana/inmunología , Leche/inmunología , Factor de Crecimiento Transformador beta/administración & dosificación , Animales , Bovinos , Enfermedad de Crohn/dietoterapia , Enfermedad de Crohn/inmunología , Femenino , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Tolerancia Inmunológica , Inmunidad Mucosa , Lactante , Recién Nacido , Mucosa Intestinal/inmunologíaRESUMEN
The coreceptor molecule, CD4, plays an integral part in T cell activation; it is involved in both extracellular Ag recognition and intracellular signaling. We wanted to examine the functional role of CD4 in the recognition of agonist and altered peptide ligands (APLs). We generated two CD4-deficient T cell lines expressing well-characterized TCRs specific for Hb(64-76)/I-Ek. Although the responsiveness of the T cell lines to the agonist peptide was differently affected by the loss of CD4 expression, the recognition of APLs was in both cases dramatically reduced. Nearly full responsiveness to the agonist peptide was achieved by expression of a CD4 variant that did not associate with p56lck; however, the stimulation by APLs was only partially restored. Importantly, the expression of a CD4 variant in which domains interacting with MHC class II molecules have been mutated failed to restore the reactivity to all ligands. CD4-deficient T cells were able to be antagonized by APLs, indicating that CD4 was not required for antagonism. Overall, these findings support the concepts that CD4 is an integral part of the initial formation of the immunological synapse, and that the requirement for different CD4 functions in T cell activation varies depending upon the potency of the ligand.
Asunto(s)
Antígenos CD4/fisiología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Animales , Antígenos CD4/biosíntesis , Antígenos CD4/genética , Antígenos CD4/metabolismo , Hibridomas , Ligandos , Activación de Linfocitos , Ratones , Péptidos/agonistas , Péptidos/genética , Péptidos/inmunología , Péptidos/metabolismo , Unión Proteica/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Transducción de Señal/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , TransfecciónRESUMEN
Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively selected on I-Ek plus self-peptides. To this pool of self-peptides we have added a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing the clonotypic TCR in the thymus and spleen. Importantly, the proliferative response of 3.L2 x A72 splenocytes is significantly reduced compared with splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral antagonism. Thus we have identified a new class of self-ligands whose predominant effect is constitutive peripheral antagonism rather than negative selection. The net effect of these ligands is to avoid potential self-reactivity while maintaining as large a repertoire as possible.
Asunto(s)
Hemoglobinas/farmacología , Tolerancia Inmunológica , Fragmentos de Péptidos/farmacología , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Células Presentadoras de Antígenos/metabolismo , Pollos , Células Clonales , Hemoglobinas/genética , Hemoglobinas/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Ligandos , Activación de Linfocitos , Recuento de Linfocitos , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C57BL , Ratones Transgénicos , Muramidasa/genética , Muramidasa/inmunología , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/biosíntesis , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Subgrupos de Linfocitos T/efectos de los fármacos , Timo/citología , Timo/inmunología , Timo/metabolismo , Transgenes/inmunologíaRESUMEN
Numerous studies have shown that a T cell can productively interact through its TCR with less-than-optimal ligands resulting in partial T-cell activation. These ligands, that we called 'altered peptide ligands' (APLs), can act as partial agonists, antagonists or weak agonists for the T cells. Here we discuss the self-antigen system that we used to provide evidence that endogenous APLs exist in vivo and affect T-cell development. We also report the ability of endogenous APLs to induce partial T-cell activation of peripheral T cells, and describe in which circumstances this could occur in vivo.
Asunto(s)
Activación de Linfocitos/efectos de los fármacos , Péptidos/inmunología , Péptidos/farmacología , Linfocitos T/inmunología , Animales , Humanos , LigandosRESUMEN
T cells potentially encounter a large number of endogenous self-peptide/MHC ligands in the thymus and the periphery. These endogenous ligands are critical to both positive and negative selection in the thymus; however, their effect on peripheral T cells has not been directly ascertained. Using the murine allelic Hbd (64-76)/I-Ek self-antigen model, we have previously identified altered peptide ligands (APLs) which are able to stimulate some but not all TCR-mediated effector functions. To determine directly the effect of endogenously synthesized APL/MHC complexes on peripheral T cells, we used a TCR transgenic mouse which had reversed our normal antigen system, with Ser69 peptide now being the agonist and Hbd(64-76) being the APL. In this report, we show that the constitutive level of endogenous Hbd(64-76)/I-Ek complexes presented by APCs in vivo is too low to affect the response of Ser69 reactive T cells. However, by increasing the number of Hbd(64-76)/I-Ek complexes expressed by the APCs, TCR antagonism is observed for both primary T cells and T cell hybridomas. In addition, the level of the CD4 coreceptor expressed on T cells and T cell hybridomas. In addition, the level of the CD4 coreceptor expressed on T cells changes the response pattern to endogenously presented Hbd(64-76)/I-Ek ligand. These findings demonstrate that T cells are selected to ignore the constitutive levels of endogenous complexes they encounter in the periphery. T cell responses can be affected by endogenous APLs in the periphery under limited but attainable circumstances which change the efficacy of the TCR/ligand interaction. Thus, endogenous APLs play a role in both the selection of T cells in the thymus and the responses of peripheral T cells.
Asunto(s)
Presentación de Antígeno , Hemoglobinas/inmunología , Activación de Linfocitos , Péptidos/inmunología , Linfocitos T/inmunología , Animales , Células Presentadoras de Antígenos , Secuencia de Bases , Antígenos CD4/metabolismo , Línea Celular , Hemoglobinas/genética , Antígenos de Histocompatibilidad/inmunología , Antígenos de Histocompatibilidad/metabolismo , Ligandos , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T alfa-beta/inmunologíaAsunto(s)
Presentación de Antígeno , Duodeno/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Biomarcadores , Antígenos CD4/inmunología , Línea Celular Transformada , Pollos , Duodeno/citología , Células Epiteliales , Epitelio/efectos de los fármacos , Epitelio/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Hibridomas/inmunología , Interferón gamma/farmacología , Interleucina-2/biosíntesis , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Antígeno-1 Asociado a Función de Linfocito/inmunología , Ratones , Ratones Endogámicos C3H , Muramidasa/inmunología , Linfocitos T/inmunologíaRESUMEN
Intestinal epithelial cells from the mouse small intestine were immortalized by SV40 large T gene transfer through a murine ecotropic virus. The resulting cell lines expressed the SV40 large T mRNA and exhibited morphological and phenotypic characteristics of normal enterocytes, including intercellular junctions, and expression of cytokeratin, villin, poly-Ig receptor (i.e., secretory component) and vasoactive intestinal peptide receptors. All expressed cell surface major histocompatibility complex class I molecules, but cell surface class II antigens were undetectable. Functional studies on antigen presentation were carried out using the MODE-K cell line established from the mouse duodenum. Interferon-gamma treatment of MODE-K cells resulted in a high level of class II molecule expression, and the ability to process and present native protein antigens to specific CD4+ T-cell hybridomas, via functional class II molecules. These data suggest that the MODE-K cell line is a suitable model for the analysis of intestinal epithelial cell function in mucosal immunity.
Asunto(s)
Transformación Celular Viral , Intestino Delgado/citología , Animales , Células Presentadoras de Antígenos/inmunología , Antígenos Virales de Tumores/genética , División Celular , Línea Celular , Células Epiteliales , Epitelio/inmunología , Epitelio/metabolismo , Expresión Génica , Antígenos de Histocompatibilidad Clase II/metabolismo , Intestino Delgado/inmunología , Intestino Delgado/metabolismo , Queratinas/genética , Ratones , Microscopía Electrónica , Fenotipo , ARN Mensajero/genética , Receptores de Péptido Intestinal Vasoactivo/metabolismo , Virus 40 de los Simios/genética , Virus 40 de los Simios/inmunologíaRESUMEN
We have examined MHC class II molecules expression by murine gut epithelial cells using a large panel of anti-Ia antibodies. In contrast to conventional APC (i.e., B cells and macrophages), only two anti-Ia antibodies reacted with enterocytes: a xenogeneic rat anti-Ia mAb (CD311) directed against a monomorphic class II determinant, and a polyclonal antiserum directed against both I-A and I-E heterodimers. In contrast, allogeneic anti-Ia mAb were either unreactive (17 of 20) or reacted weakly (3 of 20) with enterocytes, even after in vivo treatment with IFN-gamma. This pattern of Ia reactivity of epithelial cells was tissue specific (restricted to gut mucosa) and cell specific (restricted to gut epithelial cells). Biochemical and molecular studies confirmed that enterocytes expressed I-A and I-E isotypes on their cell surface and contained mRNA of both subregion loci. Interestingly, enterocytes appeared deficient in expression of the MHC class II-associated invariant chain, and are not able to stimulate allogeneic T cells. These data suggest that gut epithelial cells express a conformation of class II molecules, antigenically distinct from that expressed on conventional APC.
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Anticuerpos Monoclonales/inmunología , Antígenos de Diferenciación de Linfocitos B , Antígenos de Histocompatibilidad Clase II/inmunología , Intestinos/inmunología , Animales , Células Presentadoras de Antígenos/inmunología , Línea Celular , Epitelio/inmunología , Femenino , Antígenos H-2/inmunología , Antígenos de Histocompatibilidad Clase II/análisis , Interferón gamma/farmacología , Activación de Linfocitos , Ratones , Ratones Endogámicos C3H , Bazo/inmunología , Linfocitos T/inmunologíaRESUMEN
In previous studies, we demonstrated that intestinal epithelial cells of the mouse small intestine could present exogenous antigen to specific CD4+ T cell hybridomas. We now report on the ability of normal enterocytes to present the self superantigen Mls1a. Enterocytes from Mls1a but not from Mls1b strains stimulated interleukin-2 production through a V beta 6+ T cell hybridoma specific for Mls1a determinants. Antibody inhibition experiments showed that enterocytes presented Mls determinants via a major histocompatibility complex class II-dependent mechanism. Furthermore, the ability of enterocytes to activate V beta 6+ Mls1a-specific T cells was inhibited by monoclonal antibodies against the Orf protein encoded by an Mtv-7 provirus which is associated with Mls1a expression. These findings provide evidence for the first time that Mls determinants are expressed on normal enterocytes and support the theory of a possible role of these cells in extrathymic selection of T cell receptor V beta repertoire of intraepithelial T lymphocytes.
Asunto(s)
Intestino Delgado/inmunología , Antígenos Estimulantes de Linfocito Menor/metabolismo , Animales , Anticuerpos Monoclonales , Presentación de Antígeno , Células Epiteliales , Epitelio/inmunología , Femenino , Expresión Génica , Antígenos de Histocompatibilidad Clase II/metabolismo , Hibridomas/inmunología , Intestino Delgado/citología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos CBA , Antígenos Estimulantes de Linfocito Menor/genética , Linfocitos T/inmunologíaRESUMEN
Recent evidence has been provided for the immunological role of MHC class II molecules constitutively expressed by small intestinal epithelial cells (EC) in antigen presentation to specific T cells. Using immunohistochemical methods and antibodies to molecules expressed by dendritic cells (DC), considered as the most potent antigen presenting cell type, we observed that mature enterocytes of gut villi share common antigens with DC. Furthermore, these markers defined the heterogeneity of intestinal epithelium characterized by the presence of three EC subsets with distinct phenotype: immature crypt EC, Peyer's patch (PP) dome EC, and mature villi EC.