PubMed · 9255452
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R M Adams. Reflecting on developments in occupational dermatitis.. https://doi.org/10.1016/s0738-081x(97)00050-3
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In an attempt to develop an in vitro test to identify contact sensitizers, mostly dendritic cells (DCs) derived from monocytes (Mo-DC) have been used. Less is known about the potency of DC derived from CD34+ progenitors (CD34-DC) for in vitro allergen testing. CD34+ progenitor derived DC were exposed to nine well-known allergens (one weak, three moderate and five strong allergens) and two irritants. Surface marker expression (CD86, CD83 and HLA-DR) and cytokine production (IL-6, IL-12 and TNF-alpha) were analyzed after 24 h exposure to these chemicals. All allergens tested induced a significant increase in at least one of the DC surface markers. In contrast, none of the irritants tested were able to significantly upregulate membrane marker expression in exposed DC. The level of upregulation of CD86, CD83 and HLA-DR was dependent on the nature and concentration of the chemical, but not on the classification of the allergen. Changes in cytokine production (IL-6, IL-12 and TNF-alpha) were not consistently related to exposure to an allergen. Based on these results, we conclude that the in vitro test using CD34-DC has the capacity to distinguish between allergens and irritants based on altered phenotypic characteristics.
Murine intestinal M-cells express alpha-L-fucose residues. We constructed alpha-L-fucose-targeting particles for oral immunotherapy of IgE-mediated allergy. Poly(D,L-lactic-co-glycolic acid)-microspheres were loaded with birch pollen allergens, and functionalised with the alpha-L-fucose specific Aleuria aurantia lectin (AAL). The AAL-microspheres had a size of 1-3 microm, protected the entrapped allergens from gastric degradation and released 46.6+/-1.3% allergen over 21 days in vitro. Oral gavages of AAL-particles to naive BALB/c mice induced birch pollen-specific IgG2a, but not IgG1 antibodies. We conclude that targeting allergens to alpha-L-fucose-receptor bearing cells using AAL-microspheres induces specific Th1-antibody responses possibly counteracting Th2-dominated allergy, and therefore provides a potentially useful formulation for oral immunotherapy.
BACKGROUND: Synthetic peptides, representing CD4(+) T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. METHODS AND FINDINGS: In this study we address the mechanism of action of peptide immunotherapy (PIT) in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs) after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4(+) cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4(neg) PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4(+) and CD8(+) PBMCs. CONCLUSION: This study provides evidence for the induction of a population of CD4(+) T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.