Abstract
We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Burrows B., Martinez F. D., Halonen M., Barbee R. A., Cline M. G. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med. 1989 Feb 2;320(5):271–277. doi: 10.1056/NEJM198902023200502. [DOI] [PubMed] [Google Scholar]
- Cartier A., Thomson N. C., Frith P. A., Roberts R., Hargreave F. E. Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber. J Allergy Clin Immunol. 1982 Sep;70(3):170–177. doi: 10.1016/0091-6749(82)90038-0. [DOI] [PubMed] [Google Scholar]
- Cookson W. O., De Klerk N. H., Ryan G. R., James A. L., Musk A. W. Relative risks of bronchial hyper-responsiveness associated with skin-prick test responses to common antigens in young adults. Clin Exp Allergy. 1991 Jul;21(4):473–479. doi: 10.1111/j.1365-2222.1991.tb01688.x. [DOI] [PubMed] [Google Scholar]
- Daëron M., Prouvost-Danon A., Voisin G. A. Mast cell membrane antigens and Fc receptors in anaphylaxis. II. Functionally distinct receptors for IgG and for IgE on mouse mast cells. Cell Immunol. 1980 Jan;49(1):178–189. doi: 10.1016/0008-8749(80)90067-2. [DOI] [PubMed] [Google Scholar]
- De Souza C. M., Maia L. C., Vaz N. M. Susceptibility to cutaneous anaphylaxis in inbred strains of mice. J Immunol. 1974 Apr;112(4):1369–1372. [PubMed] [Google Scholar]
- DeKruyff R. H., Turner T., Abrams J. S., Palladino M. A., Jr, Umetsu D. T. Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor. J Exp Med. 1989 Nov 1;170(5):1477–1493. doi: 10.1084/jem.170.5.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finkelman F. D., Katona I. M., Urban J. F., Jr, Holmes J., Ohara J., Tung A. S., Sample J. V., Paul W. E. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1988 Oct 1;141(7):2335–2341. [PubMed] [Google Scholar]
- Gascan H., Gauchat J. F., Roncarolo M. G., Yssel H., Spits H., de Vries J. E. Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med. 1991 Mar 1;173(3):747–750. doi: 10.1084/jem.173.3.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holt P. G., Rose A. H., Batty J. E., Turner K. J. Induction of adjuvant-independent IgE responses in inbred mice: primary, secondary, and persistent IgE responses to ovalbumin and ovomucoid. Int Arch Allergy Appl Immunol. 1981;65(1):42–50. doi: 10.1159/000232736. [DOI] [PubMed] [Google Scholar]
- Larsen G. L., Renz H., Loader J. E., Bradley K. L., Gelfand E. W. Airway response to electrical field stimulation in sensitized inbred mice. Passive transfer of increased responsiveness with peribronchial lymph nodes. J Clin Invest. 1992 Mar;89(3):747–752. doi: 10.1172/JCI115651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lemanske R. F., Jr, Dick E. C., Swenson C. A., Vrtis R. F., Busse W. W. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions. J Clin Invest. 1989 Jan;83(1):1–10. doi: 10.1172/JCI113843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MCCAMISH J., BENEDICT A. A. STUDIES ON IMMEDIATE CUTANEOUS HYPERSENSITIVITY IN MICE. I. ACTIVE CUTANEOUS HYPERSENSITIVITY. J Immunol. 1963 Nov;91:651–651. [PubMed] [Google Scholar]
- Mohiuddin A. A., Martin R. J. Circadian basis of the late asthmatic response. Am Rev Respir Dis. 1990 Nov;142(5):1153–1157. doi: 10.1164/ajrccm/142.5.1153. [DOI] [PubMed] [Google Scholar]
- Mori A., Yamamoto K., Suko M., Watanabe N., Ito M., Miyamoto T., Okudaira H. Interleukin-4 gene expression in high and low IgE responder mice. Int Arch Allergy Appl Immunol. 1990;92(1):100–102. doi: 10.1159/000235233. [DOI] [PubMed] [Google Scholar]
- O'Byrne P. M., Dolovich J., Hargreave F. E. Late asthmatic responses. Am Rev Respir Dis. 1987 Sep;136(3):740–751. doi: 10.1164/ajrccm/136.3.740. [DOI] [PubMed] [Google Scholar]
- OVARY Z. Immediate reactions in the skin of experimental animals provoked by antibody-antigen interaction. Prog Allergy. 1958;5:459–508. [PubMed] [Google Scholar]
- OVARY Z. Passive cutaneous anaphylaxis in the mouse. J Immunol. 1958 Oct;81(4):355–357. [PubMed] [Google Scholar]
- Ovary Z., Vaz N. M., Warner N. L. Passive anaphylaxis in mice with gamma-G antibodies. V. Competitive effects of different immunoglobulins and inhibition of reactions with antiglobulin sera. Immunology. 1970 Nov;19(5):715–727. [PMC free article] [PubMed] [Google Scholar]
- Renz H., Smith H. R., Henson J. E., Ray B. S., Irvin C. G., Gelfand E. W. Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol. 1992 Jun;89(6):1127–1138. doi: 10.1016/0091-6749(92)90296-e. [DOI] [PubMed] [Google Scholar]
- Snapper C. M., Finkelman F. D., Paul W. E. Regulation of IgG1 and IgE production by interleukin 4. Immunol Rev. 1988 Feb;102:51–75. doi: 10.1111/j.1600-065x.1988.tb00741.x. [DOI] [PubMed] [Google Scholar]
- Tigelaar R. E., Vaz N. M., Ovary Z. Immunoglobulin receptors on mouse mast cells. J Immunol. 1971 Mar;106(3):661–672. [PubMed] [Google Scholar]
- Watanabe N., Ovary Z. Antigen and antibody detection by in vivo methods; a reevaluation of passive cutaneous anaphylactic reactions. J Immunol Methods. 1977;14(3-4):381–390. doi: 10.1016/0022-1759(77)90149-1. [DOI] [PubMed] [Google Scholar]