RESUMO
BACKGROUND: Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses. METHODS: In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules. RESULTS: MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1ß, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2. CONCLUSIONS: This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.
Assuntos
Dessensibilização Imunológica/métodos , Glicoproteínas/administração & dosagem , Linfócitos T/imunologia , Vacinas/administração & dosagem , Western Blotting , Citometria de Fluxo , Glicoproteínas/imunologia , Humanos , Microscopia Confocal , Reação em Cadeia da Polimerase em Tempo Real , Vacinas/imunologiaRESUMO
Aqueous solutions containing 200 mg/dm3 of p,p'-DDT and methoxychlor were photodegraded for 60 min in UV/TiO2/O2 system and chloride ions concentration and pH were measured. From 60 to 80% of the investigated pesticides were eliminated after treatment. Over 27% of chlorine atoms were splitted off for methoxychlor and 10% for p,p'-DDT. The experimental data suggest, that chlorine atoms were removed from the -CCl3 moiety but the chlorine atoms bound to aromatic ring were left intact at this step of photodegradation.