Antigen dose defines T helper 1 and T helper 2 responses in the lungs of C57BL/6 and BALB/c mice independently of splenic responses

• Published in: Immunology letters 2000-05, Vol.72 (2), p.119-126
• Main Authors: Morokata, Tatsuaki, Ishikawa, Jun, Yamada, Toshimitsu
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antigens - administration & dosage; Antigens - immunology; Cell Movement - immunology; Cytokines - biosynthesis; Dose-Response Relationship, Immunologic; Eosinophil; IFN-γ; IgE; IL-4; IL-5; Injections, Intraperitoneal; Lung - immunology; Lung - metabolism; Lung - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin - administration & dosage; Ovalbumin - immunology; Spleen - cytology; Spleen - immunology; Th1; Th1 Cells - immunology; Th2; Th2 Cells - immunology
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/S0165-2478(00)00188-7

To investigate the effect of antigen dose on immune response, C57BL/6 and BALB/c mice were sensitized with aluminum hydroxide gel (alum)-precipitated ovalbumin (OVA) then challenged with aerosolized OVA. Low-dose sensitization (less than 8 μg of OVA) elicited T helper 2 (Th2)-type immunoglobulins (Igs) secretion from C57BL/6 mice, including high levels of serum IgE, IgG1 and low levels of IgG2a, while BALB/c mice secreted T helper 1 (Th1)-type Igs, including low levels of IgE, IgG1 and high levels of IgG2a. In contrast, high-dose sensitization (more than 50 μg) elicited Th1-type Igs secretion in C57BL/6mice, while BALB/c mice exhibited Th2-type Igs secretion. Furthermore, the number of eosinophils infiltrating into the lungs of low-dose OVA-sensitized C57BL/6 mice was significantly greater than in BALB/c mice sensitized with the same amount of OVA. Only a very high dose of OVA (1 mg) could induce greater eosinophil infiltration into the lungs of BALB/c mice compared with C57BL/6 mice. Additionally, low-dose sensitization generated Th2-type cytokines, including high levels of interleukin (IL) -4, IL-5 and a low level of interferon-γ (IFN-γ) in the lungs of C57BL/6 mice, while BALB/c mice generated Th1-type cytokines in their lungs, including low levels of IL-4, IL-5 and a high level of IFN-γ. In contrast, high-dose sensitization elicited Th1-type cytokines production in the lungs of C57BL/6 mice, while BALB/c mice generated Th2-type cytokines in their lungs. Interestingly, splenocyte cultures from C57BL/6 mice produced Th1-type cytokines, while cultures from BALB/c mice produced Th2-type cytokines regardless of OVA sensitization dose (100 ng–1 mg). These results indicate that C57BL/6 and BALB/c mice have different susceptibilities to OVA-sensitization and OVA-induced pulmonary eosinophilia regulated by Th1- and Th2-type cytokines, independent of splenic Th1- and Th2-type cytokines production.