ABSTRACT
BACKGROUND: Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T cell epitopes and T cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized. OBJECTIVES: In this study, we characterized cashew-specific T cell responses in cashew-allergic subjects and examined cross-reactivity of these cashew-specific cells towards other tree nut allergens. METHODS: CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T cells were determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts. RESULTS: CD4(+) T cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T cell epitopes were then identified. These epitopes elicited either TH 2 or TH 2/TH 17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut. CONCLUSIONS: Phylogenetically diverse tree nut allergens can activate cashew-reactive T cells and elicit a TH 2-type response at an epitope-specific level. CLINICAL RELEVANCE: Lack of cross-reactivity between walnut and cashew suggests that cashew peptide immunotherapy approach may not be most effective for walnut.
Subject(s)
Allergens/immunology , Antigens, Plant/immunology , CD4-Positive T-Lymphocytes/immunology , Cross Reactions/immunology , Epitopes, T-Lymphocyte/immunology , Nuts/adverse effects , Plant Proteins/immunology , Adolescent , Adult , Amino Acid Sequence , Basophils/immunology , Basophils/metabolism , CD4-Positive T-Lymphocytes/metabolism , Child , Epitope Mapping , Epitopes, T-Lymphocyte/chemistry , Female , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Humans , Immunoglobulin E/immunology , Male , Nut Hypersensitivity/diagnosis , Nut Hypersensitivity/genetics , Nut Hypersensitivity/immunology , Nut Hypersensitivity/metabolism , Skin Tests , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Young AdultABSTRACT
Pigtail macaques (PTMs) rapidly progress to AIDS after simian immunodeficiency virus (SIV) infection. Given the strong association between human immunodeficiency virus (HIV) and SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTMs. We found that before SIV infection, PTMs had high levels of microbial translocation that correlated with significant damage to the structural barrier of the gastrointestinal tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of interleukin-17-producing T cells. These data highlight the relationship among mucosal damage, microbial translocation and systemic immune activation in the absence of SIV replication, and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTMs. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation.
Subject(s)
Intestinal Mucosa/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , T-Lymphocytes/metabolism , Acquired Immunodeficiency Syndrome/immunology , Animals , Bacterial Translocation/immunology , Disease Models, Animal , Disease Progression , HIV/immunology , Humans , Interleukin-17/biosynthesis , Lymphocyte Activation , Macaca nemestrina , T-Lymphocytes/immunology , T-Lymphocytes/pathology , T-Lymphocytes/virologyABSTRACT
A study was conducted on the influence of single and combined carriers on the dissolution rate of tolbutamide from its coprecipitates. All of the water-soluble carriers investigated enhanced the dissolution rate of tolbutamide, but the combination of 40% polyethylene glycol 6000--60% dextrose as the carrier for a 1:1 coprecipitate yielded the most rapid dissolution of tolbutamide. Other carriers used were polyethylene glycol 6000, polyethylene glycol 4000, dextrose, and mannitol, alone or combined in various proportions.
