title: Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue.
abstract: Our previous studies showed that mucosal immunity was impaired in 1-year-old mice that had been orally immunized with OVA and native cholera toxin (nCT) as mucosal adjuvant. In this study, we queried whether similar immune dysregulation was also present in mucosal compartments of mice immunized by the nasal route. Both 1-year-old and young adult mice were immunized weekly with three nasal doses of OVA and nCT or with a nontoxic chimeric enterotoxin (mutant cholera toxin-A E112K/B subunit of native labile toxin) from Brevibacillus choshinensis. Elevated levels of OVA-specific IgG Abs in plasma and secretory IgA Abs in mucosal secretions (nasal washes, saliva, and fecal extracts) were noted in both young adult and 1-year-old mice given nCT or chimeric enterotoxin as mucosal adjuvants. Significant levels of OVA-specific CD4(+) T cell proliferative and OVA-induced Th1- and Th2-type cytokine responses were noted in cervical lymph nodes and spleen of 1-year-old mice. In this regard, CD4(+), CD45RB(+) T cells were detected in greater numbers in the nasopharyngeal-associated lymphoreticular tissues of 1-year-old mice than of young adult mice, but the same did not hold true for Peyer's patches or spleen. One-year-old mice given nasal tetanus toxoid plus the chimeric toxin as adjuvant were protected from lethal challenge with tetanus toxin. This result reinforced our findings that age-associated immune alterations occur first in gut-associated lymphoreticular tissues, and thus nasal delivery of vaccines for nasopharyngeal-associated lymphoreticular tissue-based mucosal immunity offers an attractive possibility to protect the elderly.
authors.affiliation: Department of Oral Biology, Immunobiology Vaccine Center, University of Alabama, 845 19th Street South, Birmingham, AL 35294, USA.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Jerry R
authors.initials: JR
authors.lastname: McGhee
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Yoshino
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kataoka
authors.forename: Yuri
authors.initials: Y
authors.lastname: Etani
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurata
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
mesh_terms: D000281:Administration, Intranasal; D000375:Aging / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000502:physiology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012157:Mononuclear Phagocyte System / Q000276:immunology* / Q000502:physiology; D009297:Nasal Mucosa / Q000276:immunology* / Q000502:physiology; D009305:Nasopharynx / Q000276:immunology* / Q000502:physiology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010243:Paralysis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; D010047:Ovalbumin; D002772:Cholera Toxin