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H H Mu

Publications and source records attributed to H H Mu.

21 records · Page 2Linked to original sources

Regulation of DTH and IgE responses by IL-4 and IFN-gamma in immunized mice given pertussis toxin.

Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) are cytokines with important functions in regulating immune responses. IFN-gamma may be produced by cells responsible for delayed-type hypersensitivity (DTH), whereas IL-4 is essential for IgE production. Pertussis toxin (PT) from Bordetella pertussis enhances both DTH and IgE responses, and causes enhancement of both IFN-gamma and IL-4 secretion in immunized mice. In the present study, the effects of neutralizing monoclonal antibodies against IFN-gamma or IL-4 on DTH, serum IgE and cytokine production were assessed. Treatment with a monoclonal anti-IL-4 antibody at the time of immunization caused a striking increase in DTH responses, and elicited enhanced IFN-gamma expression, while inhibition of the production of IL-4 and IgE was observed. By contrast, injection of a monoclonal anti-IFN-gamma antibody was followed by significant but not complete suppression of DTH reactions. IFN-gamma secretion was also inhibited, whereas IL-4 production and serum IgE were increased. Thus antibodies to IL-4 and IFN-gamma, given at the time of immunization, can profoundly influence the nature of short-term immune responses elicited by PT in immunized mice.

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Enhancement of interleukin-4 production by pertussis toxin.

Pertussis toxin (PT), a protein toxin of Bordetella pertussis, has many biological activities, including potent adjuvant capacity and the ability to up-regulate immunoglobulin E (IgE) production. Interleukin-4 (IL-4) is a cytokine which is essential for the IgE response. Accordingly, we examined the effect of PT on IL-4 production. Spleen and lymph node cell suspensions were prepared from immunized mice and cultured with antigen or polyclonal stimuli in vitro. IL-4 secretion was assessed by bioassay, and IL-4 mRNA expression was assessed by reverse transcription and polymerase chain reaction. Significantly larger amounts of IL-4 protein and mRNA were produced in vitro by cells from mice given PT at the time of immunization than by cells from mice given antigen alone, PT alone, or the combination of antigen with cyclophosphamide. Total and antigen-specific serum IgE levels were significantly elevated in immunized mice given PT, compared with the other groups. Thus, there was a relationship between serum IgE and IL-4 production. The administration of a single dose of an anti-IL-4 monoclonal antibody in vivo, at the time of immunization and treatment with PT, abolished the development of the IgE response. These results indicate that PT is a potent stimulus for the production of IL-4, which is required for the adjuvant effect of PT on IgE formation.

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Interleukin-5 is necessary for eosinophilia induced by cyclophosphamide in immunized mice.

Interleukin-5 (IL-5) has an important role in the induction of eosinophilia, which is associated with parasitic infestations and with allergic conditions, and which can be induced in a number of experimental systems. One of these model systems involves the administration of cyclophosphamide (CY) to immunized animals. In order to assess the role of IL-5 in this model, eosinophilia was induced in vivo and cell suspensions of spleens or lymph nodes were stimulated in vitro. IL-5 protein secretion was detected by bioassay using an IL-5-dependent cell line (T88-m), and mRNA was assessed by reverse transcription and polymerase chain reaction (RT-PCR). The production of IL-5 protein and mRNA were greatly enhanced in the cells from mice given CY with ovalbumin (OVA), compared with mice given either agent alone. IL-5 protein and mRNA were increased both in spleen and in lymph node cells, and in response either to OVA or to polyclonal stimuli. Further evidence for the importance of IL-5 in this model of eosinophilia was provided by experiments with monoclonal antibodies (mAb) in vivo. A single injection of an IL-5-specific mAb at the time of immunization completely abolished the eosinophilia. By contrast, a monoclonal antibody to IL-4 had no effect. These experiments indicate that IL-5 is required for the eosinophilia induced by CY in immunized mice.

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