PubMed · 9722220
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W Burks, H A Sampson, G A Bannon. 1998. Peanut allergens.. https://doi.org/10.1111/j.1398-9995.1998.tb03967.x
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Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40(-/)- mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40(-/)- mice exhibit diminished lung inflammation, including an 80-90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.
T lymphocytes can be characterized by their pattern of cytokine secretion and be divided into type I (Th(l)/Tc(l)) and type 2 (Th(2)/Tc(2)) subsets. The involvement of type-1 or type 2-like responses in sensitization has been studied in the mouse, with reference contact and respiratory contact sensitizers. One interesting feature with certain drugs, such as beta-lactam antibiotics, is the diversity of clinical manifestations associated with immune-mediated hypersensitivity reactions in humans: immediate reactions such as urticaria, Quincke oedema and anaphylactic shock, and delayed hypersensitivity reactions, such as maculopapular rashes, allergic contact dermatitis and skin reactions of other types. In the mouse, Th(1) and Th(2) cytokines have been shown to regulate primary and secondary benzylpenicilloyl- (BPO-) specific antibody responses. Peripheral blood lymphocytes isolated from patients with a clear history of beta-lactam allergy were assessed for type-1 and type-2 phenotypes. Immediate reactions involved mixed Th(1), Tc(1), and Tc(2) responses, whereas allergic contact dermatitis involved Tc(1) and Th(1) cells. Other delayed hypersensitivity reactions to beta-lactams were restricted to Th(1) responses. It has been demonstrated that both CD4(+) and CD8(+)-lidocaine-specific T cell clones isolated from patients with allergic contact dermatitis produced IFN-gamma, even though CD8(+) clones only produce IFN-gamma, while IFN-gamma producing CD4(+) cells concomitantly produced IL-5 and IL-4. Together these data illustrate the heterogeneity of drug-specific T-cell responses.
The local lymph node assay (LLNA) is a method for the identification of skin sensitization hazard. The method is based upon measurement of proliferative responses induced in draining lymph nodes following topical exposure of mice to the test chemical. More recently the LLNA has also been used for the evaluation of relative skin sensitization potency in the context of risk assessment. Idiosyncratic drug reactions resulting from the stimulation of allergic or autoimmunogenic responses are poorly understood but represent an important clinical problem. In this article, the potential utility of the LLNA, either in a conventional modified configuration, to provide information of value in assessment the potential for systemic allergenicity is considered.