title: Alternate mucosal immune system: organized Peyer's patches are not required for IgA responses in the gastrointestinal tract.
abstract: The progeny of mice treated with lymphotoxin (LT)-beta receptor (LTbetaR) and Ig (LTbetaR-Ig) lack Peyer's patches but not mesenteric lymph nodes (MLN). In this study, we used this approach to determine the importance of Peyer's patches for induction of mucosal IgA Ab responses in the murine gastrointestinal tract. Immunohistochemical analysis revealed that LTbetaR-Ig-treated, Peyer's patch null (PP null) mice possessed significant numbers of IgA-positive (IgA+) plasma cells in the intestinal lamina propria. Further, oral immunization of PP null mice with OVA plus cholera toxin as mucosal adjuvant resulted in Ag-specific mucosal IgA and serum IgG Ab responses. OVA-specific CD4+ T cells of the Th2 type were induced in MLN and spleen of PP null mice. In contrast, when TNF and LT-alpha double knockout (TNF/LT-alpha-/-) mice, which lack both Peyer's patches and MLN, were orally immunized with OVA plus cholera toxin, neither mucosal IgA nor serum IgG anti-OVA Abs were induced. On the other hand, LTbetaR-Ig- and TNF receptor 55-Ig-treated normal adult mice elicited OVA- and cholera toxin B subunit-specific mucosal IgA responses, indicating that both LT-alphabeta and TNF/LT-alpha pathways do not contribute for class switching for IgA Ab responses. These results show that the MLN plays a more important role than had been appreciated until now for the induction of both mucosal and systemic Ab responses after oral immunization. Further, organized Peyer's patches are not a strict requirement for induction of mucosal IgA Ab responses in the gastrointestinal tract.
authors.affiliation: Department of Clinical Pathology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. fumi@mascat.nihon-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: P
authors.initials: P
authors.lastname: Rennert
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
authors.forename: M N
authors.initials: MN
authors.lastname: Kweon
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Dohi
authors.forename: S
authors.initials: S
authors.lastname: Otake
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: K
authors.initials: K
authors.lastname: Fujihashi
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004064:Digestive System / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000502:physiology; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000502:physiology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha