Mucosal Immunity in CD4-Deficient Mice: Direct Evidence for Mucosal IgA Antibody Responses

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  • Hashizume Tomomi
    Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo
  • Tanaka Shunichi
    Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo
  • Kaminogawa Shuichi
    Department of Food Science and Technology, Nihon University College of Bioresource Sciences
  • Hosono Akira
    Department of Food Science and Technology, Nihon University College of Bioresource Sciences
  • Kataoka Kosuke
    Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School
  • Shinozaki-Kuwahara Noriko
    Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo
  • Kweon Mi-Na
    Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park
  • Kurita-Ochiai Tomoko
    Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo
  • Yamamoto Masafumi
    Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo

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Abstract

CD4+ T cells and their derived cytokines are major contributors to the induction and regulation of antigen-specific antibody responses in both mucosal and systemic compartments. Past studies have shown that antigen-specific mucosal immune responses are impaired in CD4 gene-disrupted (CD4-/-) mice ; however, surface IgA+ B cells are found to co-localize to the germinal center area and CD4-CD8- (double negative) T cells replace CD4+ T cells in the Peyer's patches. Thus, we investigated whether different oral delivery systems could elicit mucosal immunity. Here we show that CD4-/- mice are capable of eliciting secretory IgA antibody responses. Oral immunization using tetanus toxoid (TT) with cholera toxin as a mucosal adjuvant resulted in mucosal IgA and serum IgG anti-TT antibody responses. Furthermore, antigen-specific T cell proliferative responses showed that significant TT-specific proliferative responses were induced in the CD4-CD8-, but not CD4-CD8+, T cells from Peyer's patches of CD4-/- mice given TT plus cholera toxin orally. These results suggest that antigen-specific mucosal IgA antibody responses may be induced by CD4-CD8- T cells in the absence of CD4+ T cells.

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