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Infection and Immunity, April 2001, p. 2328-2338, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2328-2338.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

Lisa M. Hodge,1 Mariarosaria Marinaro,2 Harlan P. Jones,1 Jerry R. McGhee,2 Hiroshi Kiyono,2,3,4 and Jerry W. Simecka1,*

Department of Molecular Biology and Immunology, University of North Texas Health Science Center in Fort Worth, Fort Worth, Texas 761071; Department of Microbiology and Immunobiology Vaccine Center2 and Department of Oral Biology,4 University of Alabama at Birmingham, Birmingham, Alabama 35294; and Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan3

Received 18 October 2000/Returned for modification 21 November 2000/Accepted 13 January 2001

The purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and lower respiratory tracts after intranasal immunization using the mucosal adjuvant cholera toxin (CT). BALB/c mice were nasally immunized with influenza virus vaccine combined with CT. The inclusion of the mucosal adjuvant CT clearly enhanced generation of antibody responses in both the nasal passages and lungs. After nasal immunization, antigen-specific immunoglobulin A (IgA) antibody-forming cells dominated antibody responses throughout the respiratory tract. However, IgG responses were significant in lungs but not in nasal passages. Furthermore, parenteral immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions, characterized by mononuclear cell infiltration, developed within the lungs of mice but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising adjuvancy. Serum IgE responses were also enhanced in a dose-dependent manner by inclusion of CT. In summary, there are differences in the generation of humoral immunity between the upper respiratory tract and the lung. As the upper respiratory tract is in a separate compartment of the immune system from that stimulated by parenteral immunization, nasal immunization is an optimal approach to generate immunity throughout the respiratory tract. Despite the promise of nasal immunization, there is also the potential to develop adverse immunopathologic reactions characterized by pulmonary airway inflammation and IgE production.

* Corresponding author. Mailing address: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107. Phone: (817) 735-2116. Fax: (817) 735-2118. E-mail: jsimecka{at}hsc.unt.edu.

Infection and Immunity, April 2001, p. 2328-2338, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2328-2338.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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