RESUMO
Leukoplakias (LPLs) are lesions in the oral mucosa that may develop into oral squamous cell carcinoma (OSCC). The objective of this study was to assess presence and distribution of dendritic Langerhans cells (LCs) and T cells in patients with LPLs with or without cell dysplasia and in oral squamous cell carcinoma (OSCC). Biopsy specimens from patients with leukoplakias (LPLs) with or without dysplasia and oral squamous cell carcinoma (OSCC) were immunostained with antibodies against CD1a, Langerin, CD3, CD4, CD8 and Ki67, followed by quantitative analysis. Analyses of epithelium and connective tissue revealed a significantly higher number of CD1a + LCs in LPLs with dysplasia compared with LPLs without dysplasia. Presence of Langerin + LCs in epithelium did not differ significantly between LPLs either with or without dysplasia and OSCC. T cells were found in significantly increased numbers in LPLs with dysplasia and OSCC. The number of CD4+ cells did not differ significantly between LPLs with and without dysplasia, but a significant increase was detected when comparing LPLs with dysplasia with OSCC. CD8+ cells were significantly more abundant in OSCC and LPLs with dysplasia compared with LPLs without dysplasia. Proliferating cells (Ki67+) were significantly more abundant in OSCC compared to LPLs with dysplasia. Confocal laser scanning microscopy revealed colocalization of LCs and T cells in LPLs with dysplasia and in OSCC. LCs and T cells are more numerous in tissue compartments with dysplastic epithelial cells and dramatically increase in OSCC. This indicates an ongoing immune response against cells with dysplasia.
Assuntos
Carcinoma de Células Escamosas/imunologia , Células de Langerhans/imunologia , Leucoplasia Oral/imunologia , Neoplasias Bucais/imunologia , Lesões Pré-Cancerosas/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Escamosas/patologia , Humanos , Imuno-Histoquímica , Células de Langerhans/patologia , Leucoplasia Oral/patologia , Microscopia Confocal , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Estatísticas não Paramétricas , Linfócitos T/patologiaRESUMO
BACKGROUND: The prevalence of self-experienced adverse reactions to foods seems to have an increasing trend in both adults and children. However, it is unclear if the prevalence of food hypersensitivity in the Swedish adult population is still rising, what symptoms are caused by different foods and which are the most common foods to which adults are more frequently IgE-sensitised. METHODS: In a cross-sectional study based on questionnaire responses, interviews and clinical examinations as part of the West Sweden Asthma Study, 1042 subjects from the general population, 17-78 years of age, living in Västra Götaland, Sweden, were included. The subjects reported symptoms for 56 specified foods and blood samples were taken to examine the IgE-sensitisation pattern for 9 common foods. RESULTS: Approximately 32% of adults reported food hypersensitivity, affecting mostly women and subjects less than 61 years old. The foods most often reported to cause adverse reactions were hazelnut (8.9%), apple (8.4%), milk (7.4%) and kiwi (7.3%). Less than one percent (0.9%) reported symptoms from ingestion of meat. Symptoms mostly affected the gastrointestinal tract (15%) and the skin (2.7%). Sixteen per cent were IgE-sensitised to common foods, most often to hazelnut (13.3%), peanut (4.9%) and almond (3.0%), while 5.9% reported symptoms and were IgE-sensitised to the same food, mainly to hazelnut (5.3%). CONCLUSIONS: The prevalence of self-reported food hypersensitivity in West Sweden indicates a rising trend. The correspondence between self-reported symptoms and IgE-sensitisation to foods is generally poor, except for hazelnut and almond which exhibit moderate or fair correlation.
RESUMO
Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
Assuntos
Vesículas Citoplasmáticas/imunologia , Hipersensibilidade/imunologia , Inflamação/imunologia , Animais , Humanos , Tolerância ImunológicaRESUMO
BACKGROUND: There is very few data available on the prevalence of food hypersensitivity among adults with asthma. The aim of this study was to explore the prevalence of self-reported adverse reactions and IgE sensitization to the different foods and to determine the spectrum and the prevalence of food-related gastrointestinal symptoms in adults with and with no asthma. METHODS: A cross sectional study based on interviews and questionnaire responses from 1527 subjects, aged 18-75 years of age, from Västra Götaland in Sweden, as part of the larger West Sweden Asthma Study. IgE analyses were performed in sera from all subjects. RESULTS: Fifty three percent of adults with asthma reported adverse reactions to foods compared to 30 % of non-asthmatics. Most asthmatics reported symptoms from eating hazelnut, followed by other nuts, birch-related foods, milk, peanut and shellfish. Furthermore, adults with asthma experienced significantly more often gastrointestinal symptoms from hazelnut, apple and milk and were found to significantly more often be sensitized to the most common foods compared to the non-asthmatic subjects. The asthmatics showed a significant correlation between IgE to both hazelnut and birch and self-reported symptoms after ingestion of hazelnut and to a lesser extent to almonds. CONCLUSIONS: The prevalence of self-reported adverse reactions and sensitization to the most common foods was much higher among the asthmatic subjects. Hazelnut was the food that asthmatics most frequently experienced adverse reactions from, and the strong correlation between IgE to hazelnut and birch indicate that the observed adverse reactions are partly due to sensitization to allergens from the PR-10 family.
RESUMO
The controlled effects of age and weaning on the numbers of CD2+ T cells, subsets (CD4+, CD8+), accessory cells (macrophage/granulocyte) and cells expressing MHC class II (DQw) and IL-2R in the piglet intestine was investigated. At birth low numbers of CD2+CD4-CD8- cells were the only demonstrable T cells in the intestine. Monocyte/granulocyte and MHC class II+ cells were also detected in low numbers and IL-2R+ cells were proportionally quite numerous. All those cell populations, except the IL-2R+ cells, increased thereafter and peaked at Week 7 when the numbers of cells were comparable with those of adult animals. CD4+ cells increased dramatically after Week 1. In contrast, CD8+ remained scarce until after 5-7 weeks of age in unweaned animals. Four days after weaning at 3 weeks old, there were increases in CD2+ (P < 0.001) and macrophage/granulocyte (P < 0.01) cells in proximal small intestinal villi and in CD2+ cells only (P < 0.01) in crypts. No significant changes in cell numbers were demonstrated in the distal small intestine.
Assuntos
Intestino Delgado/citologia , Intestino Delgado/imunologia , Suínos/imunologia , Desmame , Envelhecimento/imunologia , Animais , Subpopulações de Linfócitos B/imunologia , Antígenos CD2/análise , Feminino , Granulócitos/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Macrófagos/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Using monoclonal antibodies in immunohistochemistry, the distribution of the cells with the following surface antigens was studied in samples of proximal and distal small intestine of five 6-month-old pigs: CD2, CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T cells), accessory cell marker (monocyte/granulocyte), MHC Class II (DRw), and interleukin 2 (IL-2) receptor. CD2+ cells were found in high numbers in both the epithelium and the lamina propria. More cells were demonstrated in villis than in crypts (proportion approximately 4:1). At least two subpopulations of intraepithelial lymphocytes were identified: apically in the epithelium there were CD2+CD4-CD8- (double negative) cells, whereas cells expressing CD8 marker were concentrated around the basement membrane. CD4+ cells were localized in the lamina propria towards the villus core. Accessory cells were distributed in crypts and the villus base and more cells were found in ileum than in duodenum. In contrast, MHC Class II+ cells were located predominantly in villi, just underneath the basement membrane, forming a sheath of cells between the CD8+ and the CD4+ cells. Cells expressing IL-2 receptor were sparse but widely distributed in both the lamina propria and the epithelium. This organized cell distribution may be related to the physiology of the mucosal immune system in the gut.
Assuntos
Mucosa Intestinal/citologia , Leucócitos , Animais , Anticorpos Monoclonais , Contagem de Células , Feminino , Granulócitos/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Técnicas Imunoenzimáticas , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Masculino , Monócitos/metabolismo , Receptores de Interleucina-2/metabolismo , Suínos , Linfócitos T/metabolismoAssuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Proteínas Alimentares/imunologia , Escherichia coli/imunologia , Hipersensibilidade Tardia/imunologia , Imunoglobulina E/biossíntese , Mucosa Intestinal/imunologia , Ovalbumina/imunologia , Proteínas Recombinantes/imunologia , Linfócitos T/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/administração & dosagem , Proteínas Alimentares/administração & dosagem , Escherichia coli/metabolismo , Feminino , Adjuvante de Freund , Tolerância Imunológica , Imunidade Celular , Imunização , Imunoglobulina E/imunologia , Injeções Subcutâneas , Ovalbumina/administração & dosagem , Ovalbumina/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagemAssuntos
Animais Recém-Nascidos/imunologia , Antígenos/imunologia , Proteínas Alimentares/imunologia , Tolerância Imunológica , Imunoglobulina G/imunologia , Lactoglobulinas/imunologia , Leite/imunologia , Ovalbumina/imunologia , Fatores Etários , Animais , Especificidade de Anticorpos , Antígenos/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Imunidade Materno-Adquirida , Imunoglobulina G/biossíntese , Lactoglobulinas/administração & dosagem , Troca Materno-Fetal , Ovalbumina/administração & dosagem , Gravidez , Ratos , Ratos Sprague-DawleyAssuntos
Hipersensibilidade Imediata/embriologia , Sistema Imunitário/embriologia , Doenças do Recém-Nascido/imunologia , Troca Materno-Fetal/imunologia , Animais , Citocinas/imunologia , Desenvolvimento Embrionário e Fetal/imunologia , Feminino , Humanos , Tolerância Imunológica/genética , Recém-Nascido , Camundongos , GravidezRESUMO
In humans, the small intestinal epithelial cells (IEC) have a high constitutive expression of MHC class II (MHC II), and contains lysosomes. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes. This suggests a role for the IEC in antigen processing and presentation either directly or indirectly by the production of exosomes. However, the presence and localisation in the IEC of other key molecules involved in this process has not been studied previously. In the present work, we have investigated small intestinal biopsies from healthy adults and the HT29 IEC cell line with monoclonal antibodies against molecules involved in the antigen processing/presenting systems and molecules typically found on exosomes derived from professional APCs and IECs. Immunohistology was performed to study the expression and localisation of MHC II (HLA-DR), HLA-DM, MHC I (HLA-ABC), CD1d, Invariant chain, Lamp-1, CD68, CD63, B7.1, B7.2, ICAM-1, Cathepsin D/S/L and the IEC specific marker A33 in the IECs. We found that the IECs from the biopsies constitutively express MHC II, HLA-DM, MHC I, Invariant chain, Lamp-1, CD 68, CD63 and A33, and these markers were also found in the IFN-g treated HT-29 cells. All these molecules were found apically in the IECs of the biopsies, localised mainly in vesicular structures. Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. CD1d, B7, ICAM-1, CD9 and cathepsin D and L were absent in the IEC compartment, but cathepsin S showed a relatively weak staining in the apical part of the IEC. The staining pattern and the morphological localisation of these markers suggest a prominent antigen processing/loading and trafficking compartment, and a possible baso-lateral release of exosomes in the normal human IEC.
Assuntos
Apresentação de Antígeno , Endossomos/metabolismo , Células Epiteliais/imunologia , Mucosa Intestinal/citologia , Adulto , Idoso , Antígenos de Superfície/análise , Compartimento Celular , Endossomos/imunologia , Exocitose , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Mucosa Intestinal/imunologia , Intestino Delgado/citologia , Masculino , Pessoa de Meia-IdadeRESUMO
Fed protein undergoes processing and coupling to major histocompatibility complex (MHC) II molecules during passage through the intestinal epithelium, generating a tolerogenic form of the antigen in serum. Transfer of this factor to naïve animals induces tolerance in the recipient. In this study, we investigate what impact colonization with Gram-positive (Lactobacillus plantarum) or Gram-negative (Escherichia coli) bacteria has on tolerogenic processing in the gut. Germ-free (GF), monocolonized or conventional mice were fed ovalbumin (OVA), and their serum was collected and transferred to naïve conventional recipients that were tested for delayed-type hypersensitivity against OVA after parenteral immunization. A transferable tolerogenic factor was produced by conventional mice, but not by mice that were germ free or monocolonized with either E. coli or L. plantarum. Conventional, but neither GF nor monocolonized mice showed upregulation of MHCII expression in the epithelium of small intestine. The results suggest that a complex intestinal microflora is needed to support oral tolerance development.
Assuntos
Escherichia coli/imunologia , Tolerância Imunológica , Lactobacillus/imunologia , Administração Oral , Animais , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Soros Imunes/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Masculino , Camundongos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Organismos Livres de Patógenos Específicos , Regulação para CimaRESUMO
The immaturity of the infant's immune system and the rapid evolution of pathogens has created a demand for the mother to provide ready made specific defence factors to her offspring. This is achieved during the fetal period by transplacental transport of IgG antibodies, and after birth via IgA antibodies in the breast milk. The breast milk also contains a variety of nonspecific defence factors contributing to its antimicrobial effect. Breast feeding has been shown to decrease morbidity in gastroenteritis, septicemia, otitis media, urinary tract infection, encephalitis, pneumonia, and necrotizing enterocolitis. The antibody content in the mother's milk probably contributes not only to the immediate but also to the long term protection of the infant including both resistance to infection and development of immunological tolerance to harmless environmental antigens.
Assuntos
Anticorpos/imunologia , Mama/fisiologia , Leite Humano/imunologia , Feminino , Humanos , Imunidade Materno-Adquirida , Recém-NascidoRESUMO
14-day-old rats were orally fed with porcine colostrum or serum having a low or high activity of protease inhibitors (i.e., sow colostrum trypsin-chymotrypsin inhibitor or soybean trypsin inhibitor). The uptake of undigested porcine albumin and IgG to the blood serum of these rats was studied 4 h after feeding. The effect of the exclusion of proteases to the intestinal lumen by means of pancreatic duct ligation prior to feeding was also studied. The results from these feeding experiments in the presence of protease inhibitors or in the absence of pancreatic proteases agreed well. It was concluded that for the sucking rat the intraluminal proteolytic activity in the gastrointestinal tract is a regulator for nonselective protein uptake, as represented by albumin, while the selective absorption of IgG was unaffected.
Assuntos
Grupos de População Animal/metabolismo , Animais Lactentes/metabolismo , Proteínas Alimentares/metabolismo , Endopeptidases/fisiologia , Absorção Intestinal , Animais , Colostro/metabolismo , Feminino , Imunoglobulina G/metabolismo , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/metabolismo , Cinética , Ligadura , Pâncreas/enzimologia , Ductos Pancreáticos/fisiologia , Inibidores de Proteases/farmacologia , Ratos , Ratos Endogâmicos , Albumina Sérica/metabolismo , SuínosRESUMO
Lactating rats were given a test solution containing various marker proteins via oral or intravenous routes. Using immunoprecipitation methods for the detection of ovalbumin (OvA), bovine serum albumin (BSA), and bovine gammaglobulins (BIgG) and radioimmunoassay for the analysis of beta-lactoglobulin (beta-LG), these proteins could be found in the blood serum and the milk of the rat 6 h after administration. A specific distribution pattern between the serum and the milk was observed for each protein. The results show that orally fed dietary proteins are able to cross the gut of the lactating rat and can be found in the serum and the milk. It was also observed that oral feeding of the proteins resulted in relatively greater concentrations in the milk than did intravenous administration. This very early presentation to the young of antigenic macromolecules derived from the mother's diet might be of importance for the development of a proper immunological response to common food antigens.
Assuntos
Proteínas Alimentares/metabolismo , Absorção Intestinal , Leite/metabolismo , Ratos/metabolismo , Administração Oral , Animais , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/sangue , Feminino , Injeções Intravenosas , Leite/análise , Gravidez , Ratos Endogâmicos/metabolismoRESUMO
We have studied the development of phospholipase A2 (PLA2) and lysophosphatidylcholine (lysoPC)-metabolising enzyme activities in the neonatal rat intestine and its relation to the intestinal permeability of macromolecules. The permeability was determined by feeding young rats a mixture of bovine serum albumin, bovine immunoglobulin G and fluorescein-isothiocyanate-conjugated dextran 70,000, and analysing the serum concentrations after six hours. The animals were then killed and the intestinal mucosa was homogenised and assessed for PLA2 and lysoPC-metabolising enzyme activities. The intestine was 'open' to the macromolecules in 14 day old animals, but 'closed' in 22 and 32 day old animals and in 14 day old rats treated with cortisone acetate on day 10, 11, and 12 postpartum. The activity of PLA2 (at pH 6 and 2 mM Ca2+) was higher in 32, 22, and cortisone treated 14 day old animals, than in untreated, 14 day old animals. Incubation of 14C-acyl-lysoPC with mucosa from 14 day old rats did not change the radioactivity pattern as shown by thin layer chromatography, whereas after incubation with mucosa from 22 or 32 day old animals all the radiolabel was found in free 14C-fatty acid and in 14C-phosphatidylcholine. These findings indicate that mucosal PLA2 activity increases during intestinal maturation and that the mucosa acquires the ability to acylate and deacylate lysoPC when it is 'closed' to macromolecules.
Assuntos
Animais Recém-Nascidos/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Mucosa Intestinal/enzimologia , Lisofosfatidilcolinas/metabolismo , Fosfolipases A/metabolismo , Fosfolipases/metabolismo , Animais , Permeabilidade da Membrana Celular , Dextranos/metabolismo , Fluoresceínas/metabolismo , Imunoglobulina G/metabolismo , Absorção Intestinal , Intestinos/crescimento & desenvolvimento , Fosfolipases A2 , Ratos , Ratos Endogâmicos , Soroalbumina Bovina/metabolismoRESUMO
Guinea-pig dams and their litters were raised on either a cow's milk protein-containing diet (MCD) or a milk-free diet (MFD). At 8 weeks of age all litters were challenged i.p. with 50 micrograms milk whey-protein concentrate (V67) and 100 mg A1(OH)3 in saline. The immune response was estimated 2 weeks later as the serum IgG antibody titres against V67, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) using enzyme-linked immunosorbent assay (ELISA) and the tracheal Schulze-Dale response to these antigens. Feeding milk protein antigen to dams from birth and during pregnancy induces antigen-specific hyporesponsiveness (tolerance) in their offspring, despite no direct contact between the offspring and the milk proteins. Tolerance seems to be induced by the antigen itself since withdrawal of the MCD 10 days before delivery reduced tolerance in the offspring. No tolerance was produced in the offspring of dams fed the antigen from 3 months of age (adult). beta-LG appears to be a major antigen in milk whey while alpha-LA is a minor one since there was almost no antibody or tracheal response to alpha-LA in any of the animals tested. The results indicate that maternal antigen experience and antigens present during pregnancy are important for the subsequent immune response to these antigens in offspring.
Assuntos
Antígenos/imunologia , Tolerância Imunológica , Imunidade Materno-Adquirida , Proteínas do Leite/imunologia , Animais , Bovinos , Feminino , Cobaias , Imunoglobulina G/biossíntese , Proteínas do Leite/administração & dosagem , Gravidez , Traqueia/imunologiaRESUMO
Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Tardia/imunologia , Tolerância Imunológica/imunologia , Ovalbumina/imunologia , Anidridos Ftálicos/imunologia , Hipersensibilidade Respiratória/imunologia , Resistência das Vias Respiratórias/imunologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta Imunológica , Eosinófilos/imunologia , Haptenos/imunologia , Imunoglobulina E/análise , Imunoglobulina G/análise , Masculino , Doenças Profissionais/imunologia , Ratos , Ratos Endogâmicos BN , Valores de ReferênciaRESUMO
BACKGROUND: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker. OBJECTIVE: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). METHODS: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. RESULTS: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. CONCLUSION: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.