RESUMO
The migratory stage of Trichinella spiralis, the newborn larva, travels along the pulmonary microvascular system on its way to the striated muscle cells. In the present study, an important inflammatory reaction was observed on days 5 and 14 post-infection (p.i.) in the lungs of infected rats. This inflammation was characterized by a Th2 cell phenotype of hyperplastic bronchus-associated lymphoid tissue and by goblet cell hyperplasia. Among the inflammatory cells were eosinophils and mast cells scattered over the pulmonary parenchyma. On day 5 p.i. the number of IgE(+), CD4(+) and CD5(+) cells in the bronchus-associated lymphoid tissue were increased and IgE-secreting lung cells were also detected. At the end of the migratory phase of the infection (day 14 p.i.), only IgE(+) cells were detected in high numbers and in the bronchoalveolar lavage fluid, an increment in the total IgE levels as well as the presence of IgE and IgA anti-larvae surface were also detected. In cytotoxicity assays, cells from the bronchoalveolar lavage had considerable biological activity since they were able to kill the larvae even in the absence of specific antibodies. These results show that the lung is an organ involved in the immune response developed early during a T. spiralis infection and suggest its importance in the protection of the host.
Assuntos
Anticorpos Anti-Helmínticos/análise , Pulmão/imunologia , Trichinella spiralis , Triquinelose/veterinária , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Imunoglobulina A/análise , Imunoglobulina E/análise , Imuno-Histoquímica/veterinária , Pulmão/patologia , Ratos , Ratos WistarRESUMO
UNLABELLED: Compartmentalisation of mucosal immune response seems to be the result mainly of the preferential migration of activated cells back to their inductive sites. The aim of this report was to demonstrate, in a model of secondary immunodeficiency in Wistar rats (severely protein deprived at weaning and refed with casein 20%; group R21), that the oral administration of Thymomodulin (group:R21TmB) has different effects on gut and BALT (Bronchus-associated lymphoid tissue). Tissue sections (5 mu) were studied by immunohistochemistry 1). The oral administration of Thymomodulin restores only in gut Lamina propria (LP) the IgA B and CD4 T cell populations to control levels. The CD8a and CD25 subpopulations do not vary in gut as they return to control levels when refed with 20% casein diet. All the populations mentioned above remained decreased even after receiving Thymomodulin by the oral route. However, the same behaviour was observed for the TCR delta T cells that were decreased and return to normal levels in both mucosae by the effect of the immunomodulator; 2) when studying the iIEL (intestinal intraepithelial lymphocytes) CD8 alpha, CD25 and TCR gamma delta T cells, that were increased in R21, return to control levels in R21TmB. In BALT intraepithelium CD8 alpha and CD25 T cells remained decreased, while only TCR gamma delta T cells (increased in R21) return to control values. CONCLUSIONS: 1) there exists a compartmentalisation between both mucosae, as T CD4+ and IgA B+ cells are restored by TmB only in gut; 2) only those iIEL involved in inflammation (CD8 alpha+/CD25+ and TCR gamma delta+/CD25+) are normalised by means of the Thymomodulin 3) however, in BALT,only TCR gamma delta+ T cells are restored 4) the oral administration of the present immunomodulator may be useful as a therapeutic agent, although the preferential survival in the tissue of initial stimulation is the major factor in the preferential distribution of activated cells.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Síndromes de Imunodeficiência/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Extratos do Timo/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/imunologia , Mucosa Intestinal/patologia , Masculino , Deficiência de Proteína/complicações , Deficiência de Proteína/imunologia , Deficiência de Proteína/patologia , Ratos , Ratos Wistar , Mucosa Respiratória/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Extratos do Timo/uso terapêuticoRESUMO
Antigens presented to the immune system through the oral route induce antigen specific secretory IgA and systemic unresponsiveness, termed oral tolerance (OT). We studied the induction of OT towards a diet antigen: dextrin (DEX) in rats that underwent protein deprivation and were further re-fed. Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen (Sp) cells from protein re-fed (R) rats mediated hyporesponsiveness after transfer into naïve recipient rats. Low numbers of MLN T cells transferred hyporesponsiveness while higher numbers transferred an enhancement of the delayed type hypersensitivity (DTH) reaction. MLN T cells were further separated based on their ability to bind Vicia villosa (VV). MLN VV- T cells, mainly CD8+, mediated hyporesponsiveness and MLN VV+ T cells (CD45RC+ CD4- CD8- cells) abrogated the hyporesponsiveness. Moreover, Sp DEX adherent T cells were mainly CD8+. Intestinal intraepithelial lymphocytes (iIELs) mainly CD8alpha+ gamma(delta)-TCR+ cells also inhibited the DTH response to DEX after transfer. The positive DTH response to another carbohydrate (levan) indicates the specificity of the suppression to dextrin. Therefore, our data indicate that after oral administration of DEX, two different populations of T cells were generated: one found only in the MLN that mediated DTH responses and the other one capable of migrating from the intestinal intraepithelium through PP and MLN to the Sp, mediating systemic tolerance.
Assuntos
Dextrinas/imunologia , Linfócitos T Reguladores/fisiologia , Administração Oral , Animais , Movimento Celular , Dieta , Intestinos/citologia , Linfonodos/citologia , Masculino , Deficiência de Proteína/imunologia , Deficiência de Proteína/fisiopatologia , Ratos , Ratos WistarRESUMO
The effect of severe protein deficiency at weaning has been studied in bone marrow, which is a primary lymphoid organ. Our experimental model of secondary immunodeficiency in Wistar rats has shown: (1) a decreased number of viable bone marrow cells (P <.0001); (2) diminished percentage of mitosis (P <.01); and (3) severe alteration in the percentage of chromosome pairs 3, 11, and 12 bearing nucleolar organizer regions (NORs) (P <.05). This last finding indicates a poor ribosomal gene activity. These alterations were reverted after the oral administration of a 20% casein diet during 5 to 9 days. However, there were no karyotype variations between the experimental groups. We conclude from these results that severe protein deficiency at weaning alters several aspects of bone marrow cell proliferation and ribosomal gene activity as determined by the number of silver stained nucleolus organizer regions.
Assuntos
Células da Medula Óssea/patologia , Distúrbios Nutricionais/patologia , Deficiência de Proteína/patologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Caseínas/administração & dosagem , Contagem de Células , Aberrações Cromossômicas/genética , Feminino , Cariotipagem , Masculino , Metáfase/genética , Mitose/genética , Índice Mitótico , Região Organizadora do Nucléolo/patologia , Distúrbios Nutricionais/complicações , Distúrbios Nutricionais/dietoterapia , Deficiência de Proteína/complicações , Deficiência de Proteína/dietoterapia , Ratos , Ratos Wistar , Coloração pela PrataRESUMO
OBJECTIVES: We studied the effect of a low-quality dietary protein on cellular proliferation and maturation in the thymus of growing rats over time. METHODS: After weaning Wistar rats were fed a diet containing 6.5 g/100 g of corn flour for 6, 10, 18, and 45 d (M groups). For comparison, other rats were fed a diet containing 6.5 g/100 g of casein (Cas groups), and well-nourished age-matched control rats were fed a commercial laboratory diet (C groups). Food intake, body weight, thymus weight, total number of thymocytes, and the percentages of CD43(+) and Thy1(+) thymocyte phenotypic antigen determinants were measured. RESULTS: M versus Cas and C groups showed significant differences (P < 0.01) in body and thymus weights after 6 d of feeding, and the total number of thymocytes and the percentages of CD43(+) and Thy1(+) were significantly lower after 10 d of feeding. The results indicated that consuming a cereal diet for short or long periods causes thymus atrophy in growing rats, with significant reductions in the total number of T-cells concomitant with increases in the number of immature thymocytes. CONCLUSIONS: The data showed that, in addition to low-protein concentration, low-quality dietary protein is a limiting factor in certain steps of cellular intrathymic pathways, probably related to the requirement of specific amino acids for optimal immune response.
Assuntos
Antígenos CD , Proteínas Alimentares/administração & dosagem , Distúrbios Nutricionais/imunologia , Deficiência de Proteína/patologia , Linfócitos T/imunologia , Timo/crescimento & desenvolvimento , Animais , Biomarcadores , Peso Corporal/imunologia , Caseínas/administração & dosagem , Caseínas/normas , Proteínas Alimentares/normas , Ingestão de Alimentos , Feminino , Leucossialina , Contagem de Linfócitos , Masculino , Distúrbios Nutricionais/fisiopatologia , Valor Nutritivo , Tamanho do Órgão/imunologia , Fenótipo , Ratos , Ratos Wistar , Sialoglicoproteínas/análise , Sialoglicoproteínas/imunologia , Antígenos Thy-1/análise , Antígenos Thy-1/imunologia , Timo/citologia , Timo/imunologia , Timo/patologia , Zea mays/normasRESUMO
En 1994 en un estudio realizado por nuestro grupo en colabaración con la Dra. Fuksman sobre 1.200 placentas correspondientes a embarazos de alto riesgo, se halló la presencia de villitis en el 5.6 por ciento de las mismas. La histopatología detectada en ese momento fue deciduitis linfocitaria y aumento de fibrina perirvellositaria asociada con hipoirrigación e infarto placentario. Hallamos que en el 55 por ciento de las placentas con villitis los recién nacidos presentaban RCIU con respecto al 10 por ciento de los controles, con un PA de 32 por ciento en las villitis y el 83 por ciento en los controles (3). En ese material se estudiaron 68 placentas con villitis y 68 placentas sin villitis como grupo control. En 1996 demostramos en ese mismo material mediante la técnica de anticuerpos monoclonales, sobre cortes de placenta estudiando las subpoblaciones linfocitarias de las villitis, que el 50 por ciento eran CD4 (linfocitos helper), 18 por ciento CD8 (linfocitos supresoreslcitotóxicos) y 10 por ciento Leu19 (Natural Killer) pero lo significativo y anormal es que hallamos que el 65 por ciento de los linfocitos expresaban antígenos de histocompatibilidad clase II DR (40). En 1998 Jacques y Col publicaron datos similares. En 1999 comunicamos que en el informe histopatológico de material de legrado de pacientes abortadoras de causa inmunológica la descripción de villitis en un 20 por ciento de los casos. Estudios realizados en colabaración con la Dra. Zenclussen con ese material nos permitió publicar recientemente la presencia de altos niveles de Interleuquina 6(IL-6) y receptor de IL-6 en suero. El objetivo de este estudio es investigar en placentas de pacientes abortadoras recurrentes la expresión de IL-6 y sus receptores gp80 y gp130 en trece muestras de material de raspado de abortos del primer trimestre mediante la técnica de inmunofluorescencia. Como control se utilizaron cortes de placentas de embarazos normales a término. Nuestros hallazgos muestran la presencia de depósitos de IL-6 y de receptores de IL-6 con un patrón granular para las tres moléculas especificamente en el sinciciotrofoblasto mientras que fue negativo para tres en el citotrofoblasto. En los cortes de placentas normales no se hallaron en ningún caso dichos depósitos. Concluímos de todos los hallazgos antes sintetizados...(AU)
Assuntos
Humanos , Recém-Nascido , Feminino , Gravidez , Aborto Espontâneo/etiologia , Placenta/patologia , Trofoblastos/patologia , Interleucina-6/efeitos adversos , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Aborto Espontâneo/imunologia , Anticorpos Monoclonais/diagnóstico , Antígenos de Histocompatibilidade , Antígenos de Histocompatibilidade Classe II , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Decídua/patologia , Receptores de Interleucina-6/imunologia , Imuno-Histoquímica , Gravidez de Alto Risco/imunologia , Corioamnionite/imunologia , Corioamnionite/fisiopatologiaRESUMO
En 1994 en un estudio realizado por nuestro grupo en colabaración con la Dra. Fuksman sobre 1.200 placentas correspondientes a embarazos de alto riesgo, se halló la presencia de villitis en el 5.6 por ciento de las mismas. La histopatología detectada en ese momento fue deciduitis linfocitaria y aumento de fibrina perirvellositaria asociada con hipoirrigación e infarto placentario. Hallamos que en el 55 por ciento de las placentas con villitis los recién nacidos presentaban RCIU con respecto al 10 por ciento de los controles, con un PA de 32 por ciento en las villitis y el 83 por ciento en los controles (3). En ese material se estudiaron 68 placentas con villitis y 68 placentas sin villitis como grupo control. En 1996 demostramos en ese mismo material mediante la técnica de anticuerpos monoclonales, sobre cortes de placenta estudiando las subpoblaciones linfocitarias de las villitis, que el 50 por ciento eran CD4 (linfocitos helper), 18 por ciento CD8 (linfocitos supresoreslcitotóxicos) y 10 por ciento Leu19 (Natural Killer) pero lo significativo y anormal es que hallamos que el 65 por ciento de los linfocitos expresaban antígenos de histocompatibilidad clase II DR (40). En 1998 Jacques y Col publicaron datos similares. En 1999 comunicamos que en el informe histopatológico de material de legrado de pacientes abortadoras de causa inmunológica la descripción de villitis en un 20 por ciento de los casos. Estudios realizados en colabaración con la Dra. Zenclussen con ese material nos permitió publicar recientemente la presencia de altos niveles de Interleuquina 6(IL-6) y receptor de IL-6 en suero. El objetivo de este estudio es investigar en placentas de pacientes abortadoras recurrentes la expresión de IL-6 y sus receptores gp80 y gp130 en trece muestras de material de raspado de abortos del primer trimestre mediante la técnica de inmunofluorescencia. Como control se utilizaron cortes de placentas de embarazos normales a término. Nuestros hallazgos muestran la presencia de depósitos de IL-6 y de receptores de IL-6 con un patrón granular para las tres moléculas especificamente en el sinciciotrofoblasto mientras que fue negativo para tres en el citotrofoblasto. En los cortes de placentas normales no se hallaron en ningún caso dichos depósitos. Concluímos de todos los hallazgos antes sintetizados...
Assuntos
Humanos , Recém-Nascido , Feminino , Gravidez , Aborto Espontâneo/etiologia , Interleucina-6/efeitos adversos , Placenta/patologia , Trofoblastos/patologia , Aborto Espontâneo/imunologia , Anticorpos Monoclonais , Antígenos de Histocompatibilidade Classe II , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Corioamnionite/imunologia , Corioamnionite/fisiopatologia , Decídua/patologia , Antígenos de Histocompatibilidade , Imuno-Histoquímica , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Gravidez de Alto Risco/imunologia , Receptores de Interleucina-6/imunologiaRESUMO
BACKGROUND: We have shown, in a rat model of immunodeficiency, permanent alterations in the thymus and in the gut-associated lymphoid tissues. We observed by immunohistochemistry an increase in the number of gamma/delta+ T cells in the gut lamina propria and in the number of CD8alpha/alpha+, CD25+, gamma/delta+ subpopulations of intestinal intraepithelial lymphocytes (iIEL). The aim of the present study was to analyze the isolated rat iIEL by flow cytometry. Materials and Methods Cells from mesenteric lymph nodes were examined in parallel with isolated iIEL. After staining with different antibodies, samples were run on a FACScan flow cytometer. Background staining was evaluated using isotype controls. Data analysis was performed using Lysys II software (Becton Dickinson) and WinMDI 2.3 software. RESULTS: 1) CD8alpha/beta populations do not express TCRgamma/delta, 2) CD8alpha/alpha+ populations express TCRgamma/delta, and its percentage is significantly increased in R21, 3) CD8alpha/beta and CD8alpha/alpha iIEL express TCRalpha/beta, being the percentage of CD8alpha/alpha+ TCRalpha/beta+ iIEL increased and the percentage of CD8alpha/beta+ TCRalpha/beta+ iIEL decreased in R21, and 4) CD8alpha/alpha as well as CD8alpha/beta iIEL do express CD25 only in R21. CONCLUSIONS: Considering the above results, we conclude that there exists an "in situ" origin and extrathymic maturation of the CD8alpha/alpha+ iIEL in the intestinal epithelium. The increase of TCRgamma/delta+ T cells may be triggered by the carbohydrate dextrin, to provide immune protection and control of inflammation at the intestinal level.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Citometria de Fluxo , Hospedeiro Imunocomprometido , Intestinos/imunologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Epitélio/imunologia , Feminino , Intestinos/citologia , Linfonodos/citologia , Masculino , Deficiência de Proteína/imunologia , Ratos , Ratos Wistar , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Subpopulações de Linfócitos T/imunologiaRESUMO
The aim of the present report was to study in growing Wistar rats the development of immunocompetent cells in the bronchus-associated lymphoid tissue (BALT). We found at day 4 postpartum, a high number of TCRgamma/delta+ T cells and very few CD8alpha+, CD8beta+, CD5+, TCRalpha/beta+ T cells in BALT. The latter cells and CD4+ T cells increase with age. Even though T cells expressing TCRgamma/delta outnumber those expressing TCRalpha/beta early in development, until 45 days of age, alpha/beta+ predominate over gamma/delta+ T cells only in adult rats (60 days of age). Moreover, a predominance of suppressor/cytotoxic T cells over T-helper cells was found in 60 days old rats. Surprisingly, more CD8alpha+ than CD8beta+ T cells in BALT are observed. The number of IgA+ B and CD4+ T cells found in the BALT increases with age. The early appearance - 4 days of age - of all T-cell phenotypes in BALT especially of gamma/delta+ T cells may imply a benefit to respond to inhaled antigen soon after birth.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/imunologia , Brônquios/citologia , Brônquios/imunologia , Imunocompetência , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Envelhecimento/imunologia , Animais , Animais Recém-Nascidos/anatomia & histologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Brônquios/crescimento & desenvolvimento , Antígenos CD4/biossíntese , Antígenos CD5/biossíntese , Imunoglobulina A/biossíntese , Imuno-Histoquímica , Tecido Linfoide/crescimento & desenvolvimento , Ratos , Ratos Wistar , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Receptores de Antígenos de Linfócitos T gama-delta/biossíntese , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Previous studies on the effect of the oral administration of bacterial immunomodulators (1M-104 and RN-301) during the protein free diet period, have shown an increase on B and T cell gut repopulation, accompanied by IgA antibody production. The usefulness of oral administration of the immunomodulator thymomodulin (TmB) during the protein refeeding period was investigated. TmB allowed the recovery of a normal repopulation of gut lamina propria with IgA B and CD5 T cells and decreases to control values the number of activated intraepithelial lymphocytes (CD25+ T cell subset). Therefore, the oral administration of TmB may be useful as a therapeutic agent as it seems to improve the repopulation of intestinal villi with immunocompetent cells. Also, it seems to regulate the immunosurveillance at the epithelium level as it increases the CD5+ T cells but decreases the activated ones.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Imunoglobulina A/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Deficiência de Proteína/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Extratos do Timo/uso terapêutico , Análise de Variância , Animais , Linfócitos B/metabolismo , Caseínas , Feminino , Imunoglobulina A/metabolismo , Intestinos/citologia , Masculino , Deficiência de Proteína/metabolismo , Ratos , Ratos Wistar , Linfócitos T/metabolismoRESUMO
It has been previously demonstrated in Wistar rats that severe protein deprivation at weaning, even after refeeding with a 20% casein diet for 21 days, provokes alterations in IgA+ B cell and T cell populations from gut and GALT (gut associated lymphoid tissue) that are reverted by immunomodulator IM-104. In the present report, we investigate the influence of RN-301 (quite similar to IM-104) given by the oral or subcutaneous route during the protein deprivation period, in the seeding of BALT with IgA+ B and CD5+ T cells. The immunomodulator RN-301 contains LPS from E. coli and membrane and ribosomal fractions of P. acne. Tissue sections of the lower respiratory tract were studied by immunohistochemistry. The immunomodulator RN-301 administered by the oral route favours the significant increase in the seeding of the BALT lamina propria with IgA+ B and CD5+ T cells (p < 0.001). However, the RN-301 given by the subcutaneous route does not favour the repopulation of the BALT lamina propria. The ribosomal fractions from P. acne associated with LPS from E. coli contained in the immunomodulator RN-301 administered by the oral route may rescue the small resting lymphocytes in the gut-associated lymphoid tissue (GALT). This event favours their proliferation and migration to the BALT.
Assuntos
Adjuvantes Imunológicos/farmacologia , Dieta com Restrição de Proteínas , Tecido Linfoide/efeitos dos fármacos , Desmame , Animais , Feminino , Masculino , Compostos Orgânicos , Ratos , Ratos WistarRESUMO
Attempts to achieve IgA responses in the intestine by oral immunization with non replicating antigens have been characterized by ineffective responses of short duration unless long term dosages are administered. Cholera toxin (CT) is an exception in that it is able to produce a high secretory and systemic immune response. We study the effects of a bacterial immunomodulator [3 x 10(10) Propionibacterium granulosum ml-1 and lipopolysaccharide (LPS) 5 mg ml-1] on the immune response to CT orally administered to Wistar rats. The immunomodulator was orally administered as follows: in schedule 1 during 7 days prior to the first dose of CT; and in schedule 2, 2 days before, together, and 3 days after the first dose of CT. Schedules 1 and 2 were effective in increasing the specific IgA in the intestinal fluid and specific IgG in serum (P < 0.001) when compared to controls. Besides, schedule 2 was more effective than schedule 1 when the levels of specific IgG in serum or specific IgA in intestinal fluid was measured (P < 0.05). Total IgA in the intestinal fluid was increased in rats receiving the immunomodulator (P < 0.01). However, the ratio of specific IgA per total IgA was higher in rats receiving treatment 1 or 2 when compared to controls (P < 0.01). The number of antitoxin antibody producing cells was not increased in the Peyer patches, but a significant increase was observed in the mesenteric lymph nodes and spleen when compared to controls (P < 0.05). The administration of LPS alone produced an increase in the antitoxin immune response when compared to controls, but it was lower than those produced by the administration of the immunomodulator. These results indicate that this immunomodulator is an effective adjuvant of the mucosal and systemic immune response to CT. The mechanisms of action possibly involve nonespecific and specific modulations of the immune response.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Toxina da Cólera/administração & dosagem , Propionibacterium/imunologia , Administração Oral , Animais , Anticorpos/análise , Anticorpos/sangue , Líquido da Lavagem Broncoalveolar/imunologia , Toxina da Cólera/imunologia , Intestinos/imunologia , Ratos , Ratos Wistar , Baço/imunologiaAssuntos
Anticorpos Antibacterianos/biossíntese , Toxina da Cólera/imunologia , Imunoglobulina A/biossíntese , Imunoglobulina M/biossíntese , Síndromes de Imunodeficiência/imunologia , Intestino Delgado/imunologia , Contagem de Linfócitos , Tecido Linfoide/imunologia , Distúrbios Nutricionais/imunologia , Vibrio cholerae/imunologia , Animais , Animais Lactentes , Linfócitos B/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Dieta , Síndromes de Imunodeficiência/etiologia , Intestino Delgado/patologia , Tecido Linfoide/patologia , Distúrbios Nutricionais/complicações , Distúrbios Nutricionais/dietoterapia , Ratos , Ratos WistarAssuntos
Síndromes de Imunodeficiência/imunologia , Mucosa Intestinal/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Anticorpos Monoclonais , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Imunidade nas Mucosas , Síndromes de Imunodeficiência/patologia , Mucosa Intestinal/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Ratos , Ratos Wistar , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Antígenos Thy-1/metabolismoRESUMO
Previously we found that malnutrition during lactation in rats produces an impairment in the immune response to cholera toxin. In this report we found that malnutrition during lactation provokes in 28-day-old rats an increase of Thy1+ c mu+ cells in gut associated lymphoid tissues concomitantly with a decrease of sIgA+ B cells. No differences were found in the percentages of the IgM+ B cell populations. Furthermore, no differences were found in the Peyer's patch (PP) and mesenteric lymph node (MLN) T cell subsets in weaning rats when compared to controls. However, after 1 week of refeeding a higher percentage of the Thy1+ c mu- subset together with a lower percentage of CD5+, CD4+, and CD8+ T cells, were found in malnourished rats when compared to controls. The above results may indicate that B-cell maturation is delayed in malnourished rats at two stages of differentiation: (a) in the passage of pre-B cells (Thy1+ c mu+) to immature B cells (s mu+), and (b) in the switch from s mu+ B cells to s alpha+ B cells. The decrease of CD5+, CD4+, and CD8+ T cells together with an increase of the Thy1+ c mu- subset in gut-associated lymphoid tissues (GALT) may indicate that T-cell maturation is also delayed. Results obtained at weaning may be due to an engraftment by maternal milk-derived lymphocytes in the pups.
Assuntos
Animais Lactentes/imunologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Distúrbios Nutricionais/imunologia , Linfócitos T/imunologia , Animais , Células Cultivadas , Feminino , Imunofenotipagem , Mucosa Intestinal/imunologia , Lactação/imunologia , Linfonodos/imunologia , Microscopia de Fluorescência , Ratos , Ratos WistarRESUMO
Malnourished rats during suckling were orally immunized with cholera toxin (CT) after different periods of refeeding. Intestinal fluids, sera, and supernatant fluids from cultured mesenteric lymph node (MLN) cells were obtained after rats were given three doses of CT and analyzed by enzyme-linked immunosorbent assay (ELISA) to evaluate the specific antibody response. Serum-specific immunoglobulin G (IgG), IgA, and IgM were severely diminished in malnourished rats immunized with three doses of CT after 1 week of refeeding when compared with those of controls. Also, a decreased IgA ELISA titer of the intestinal fluids and abrogation of the capacity to neutralize the CT in the intestinal ligated loop test were found. When a booster was given at 113 days of age, the immune response continued to be affected in the serum and the intestinal fluid. The results from the analysis of the supernatant fluids from cultured MLN cells were coincident with those mentioned above. When one dose of CT was administered into Peyer's patches (PP) after 1 week of refeeding, an impaired immune response was found in the intestinal fluid of malnourished rats during suckling compared with that of controls. This result together with the analysis of supernatant from MLN and PP cell cultures suggests that antigen triggering in the PP was affected. When the refeeding period was extended to 30 days and then the first dose of CT was administered, the antibody immune responses in intestinal fluid serum and supernatant fluid approached control values. These observations reinforce the fact that the gut-associated lymphoid tissue immaturity of the rats when they received the first CT dose (at 28 days old) was the main reason for the decreased immune response observed in the experimental group.
Assuntos
Animais Lactentes/imunologia , Anticorpos Antibacterianos/metabolismo , Toxina da Cólera/administração & dosagem , Distúrbios Nutricionais/imunologia , Administração Oral , Animais , Formação de Anticorpos , Peso Corporal , Feminino , Imunoglobulina A/metabolismo , Intestinos/imunologia , Linfonodos/imunologia , Masculino , Mesentério , Nódulos Linfáticos Agregados/imunologia , Ratos , Ratos WistarRESUMO
In this report we present data that help to define the impact of malnutrition during the suckling period on the gut associated lymphoid tissues (GALT). Fifty-day old rats malnourished during lactation presented a diminished percentage of s alpha +B cells and IgA level in the intestinal fluid. Also, a decrease in the CD4+ and CD8+ T cell subsets was found. At 120 days of age the percentage of s alpha +B cells and IgA level in the intestinal fluid was similar to the control. However, the percentage of T cells remained altered. When three doses of chorea toxin were administered orally since day 28, the IgA anti CT antibodies were diminished in the intestinal fluid, while the immunization schedule started after seven days of refeeding (28 days of age). This impairment of the immune response remained even after a CT booster was given to animals 113 days old. This diminishing in the CD4+ T cells may be the major cause of the nonresponsiveness described herewith.
Assuntos
Lactação/imunologia , Tecido Linfoide/imunologia , Distúrbios Nutricionais/fisiopatologia , Animais , Toxina da Cólera/imunologia , Feminino , Imunoglobulina A/análise , Imunoglobulina G/análise , Contagem de Leucócitos , Estudos Longitudinais , Linfonodos/imunologia , Linfócitos , Masculino , Nódulos Linfáticos Agregados/imunologia , Ratos , Ratos WistarRESUMO
The aim of this study is to characterize intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), as well as IgA B cells in the intestinal villi of the small intestine of rats which were fed a protein free diet (PF) and of those which were refed a 20% casein diet for 21 days (R21). Age matched control groups are also analyzed. T cell subsets and IgA-B cells were studied in tissue sections by the immunofluorescence technique. Lamina propria (LP) of the small intestine of the PF group were almost devoid of IgA-B cells; in the R21 group, the number of IgA-B cells was significantly diminished, when compared to the control group. The number of LPL in R21 group was not significantly different from the control group. W3/25+ (CD4) IEL diminished significantly in the intestinal villi of R21 group, while OX8+ (CD8) and OX22+ (CD45R) IEL were significantly increased when compared to the control group. These results indicate that: 1) Protein deficiency provokes an impairment of IgA-B cell terminal differentiation. 2) There is repopulation of LP by T cells in the R21 group. 3) The increased number of OX8+ (CD8) and OX22+ (CD45R) IEL might permit induction of intestinal delayed type hypersensitivity, thereby abrogating oral tolerance of systemic delayed type hypersensitivity.
Assuntos
Imunoglobulina A/análise , Intestino Delgado/imunologia , Linfócitos/imunologia , Deficiência de Proteína/imunologia , Envelhecimento , Animais , Linfócitos B/imunologia , Hospedeiro Imunocomprometido , Ratos , Ratos Endogâmicos , Subpopulações de Linfócitos T/imunologia , DesmameRESUMO
Terminal deoxynucleotidyl transferase (TdT) containing cells were found in the mesenteric lymph nodes of protein deprived and casein re-fed rats. Double immunofluorescence was used to characterize these TdT+ cells according to their surface antigenic phenotype. TdT+ cells expressing T-cell antigen markers recognized by monoclonal antibodies: W3/13 and OX-19 indicated thymic origin. It was found that these cells represented half the existing TdT+ population in the mesenteric lymph nodes. The rest of them presented the Ia antigen which is coded for by the class II major histocompatibility complex and is recognized by the OX-6 mAb. TdT+ cells presenting the OX-6+ phenotype were ascribed to a bone marrow derived subset. These results indicate that, in some instances, i.e., immunodeficiency due to protein deprivation, TdT+ cells may appear in the mesenteric lymph nodes. Their origin may be attributed either to trafficking of immature cells from the thymus or to cells that leave the bone marrow as a consequence of the damage provoked by protein deprivation.
Assuntos
Antígenos/genética , DNA Nucleotidilexotransferase/biossíntese , Imunidade , Linfonodos/enzimologia , Linfócitos Nulos/enzimologia , Mesentério/imunologia , Distúrbios Nutricionais/imunologia , Animais , Animais Lactentes , Feminino , Linfonodos/metabolismo , Masculino , Mesentério/enzimologia , Fenótipo , Ratos , Ratos EndogâmicosRESUMO
The status of the thymus of growing rats fed for 45 days after weaning on a low-quality dietary protein (7.5% maize) was compared with that in an age-matched control group receiving a diet containing casein at the same concentration. At the end of the feeding period, body weight (bw) was determined and the thymus was removed; its weight and cell number and the mature T-cell population--characterized by the monoclonal antibody W3/13 using the indirect immunofluorescence technique--were determined. Thymus weight expressed as mg/bw0.75 (3.9 +/- 0.75 vs 7.7 +/- 2.0), cell number (4.4 +/- 2.2 vs 26.3 +/- 7.6), and the absolute number of W3/13+ T cells (1.59 +/- 0.75 vs 17.8 +/- 5.4) were significantly lower (p less than 0.0005) in the experimental group than in the control group. The results suggest severe atrophy of the thymus of weaning animals chronically fed a low-quality protein.