Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue.
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.
Hagiwara
Yukari
Y
Department of Oral Biology, Immunobiology Vaccine Center, University of Alabama, 845 19th Street South, Birmingham, AL 35294, USA.
McGhee
Jerry R
JR
Fujihashi
Keiko
K
Kobayashi
Ryoki
R
Yoshino
Naoto
N
Kataoka
Kosuke
K
Etani
Yuri
Y
Kweon
Mi-Na
MN
Tamura
Shinichi
S
Kurata
Takeshi
T
Takeda
Yoshifumi
Y
Kiyono
Hiroshi
H
Fujihashi
Kohtaro
K
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
D016207:Cytokines; D007070:Immunoglobulin A; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; D010047:Ovalbumin; D002772:Cholera Toxin