0000000000190949
AUTHOR
E. R. Jarman
Induction of regulatory T cells by leflunomide in a murine model of contact allergen sensitivity.
Allergic contact dermatitis and contact hypersensitivity (CHS) are characterized by allergen-specific activation of CD8 + and CD4 + T cells and the production of cytokines resulting in an inflammatory response and tissue damage. We show here that the immunosuppressive compound leflunomide ( N -[4-trifluoro-methylphenyl]-5-methylisoxazol-4 carboxamide, HWA 486) (LF) inhibited the contact allergic response induced in mice by epicutaneous application of the haptens dinitrofluorobenzene (DNFB) and oxazolone. The extent of ear swelling remained significantly reduced following repeated challenge with DNFB for up to 18 weeks. LF and DNFB had to be applied simultaneously for inhibition to occur. Th…
Inhibition of murine IgE and immediate cutaneous hypersensitivity responses to ovalbumin by the immunomodulatory agent leflunomide
SUMMARYLeflunomide has been identified as an immunoregulatory and anti-inflammatory compound. Allergic disease is characterized by elevated serum IgE levels, production of allergen-specific IgE and the release of inflammatory mediators from mast cells and granulocytes. Here we demonstrate, using an in vivo murine model, the ability of leflunomide to down-regulate levels of total and allergen-specific serum IgE production. Mice receiving leflunomide (45 mg/kg) orally at the time of primary immunization with ovalbumin adsorbed to aluminium hydroxide adjuvant, showed a reduction in total serum IgE levels of 95%, 41% and 32% following primary, secondary and tertiary immunizations, respectively …
Deficient cytokine response of human allergen-specific T lymphocytes from humanized SCID mice and reconstitution by professional antigen-presenting cells.
Abstract Background: Hu-PBL-SCID mice generated by the transfer of PBMCs from atopic individuals may provide a physiologic in vivo model for investigating human responses to allergens and potential approaches toward immunotherapy. Objective: This study was undertaken to investigate the functional activity and cytokine profile of human allergen-reactive T lymphocytes isolated from hu-PBL-SCID mice. Methods: PBMCs from allergic individuals were coinjected with allergen into SCID mice. Human lymphocyte migration and phenotype were established by reverse transcription–PCR and immunohistochemistry, IgE levels in sera were determined, and the frequency of allergen-reactive cytokine-producing T ly…
Short-term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T-cell responses, in patients with allergic rhinitis
Backround Birch pollen allergic rhinitis can be sufficiently treated with specific subcutaneous allergoid immunotherapy (IT). However, little is known about the clinical and immunological effects of short-term therapy protocols. Objective To investigate the clinical efficacy of a birch pollen allergoid IT using seven preseasonal injections and to evaluate immunological parameters that might explain clinical findings. Methods Thirty-seven patients were included into the study and randomized to either a symptomatic treatment or allergoid IT plus symptomatic treatment. Patients were examined during the pre-IT season, at two extraseasonal visits both before and after IT and during the post-IT s…
Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids)
Background Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases. Objective The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes. Methods Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch polle…