Development of antibody-secreting cells and antigen-specific T cells in cervical lymph nodes after intranasal immunization.
Intranasal (i.n.) immunization with bacterial protein antigens coupled to cholera toxin B subunit (CTB) effectively induces mucosal, especially salivary immunoglobulin A (IgA), and nonmucosal antibody responses in mice. To examine the regional distribution of antigen-specific B and T cells after i.n. immunization, antibody-secreting cells and antigen-responsive T cells in cervical lymph nodes (CLN) were compared with those found after intraoral or subcutaneous (in the neck) administration of the same antigen and with T cells found in mesenteric lymph nodes (MLN) and spleen after intragastric immunization. The i.n. immunization induced predominantly IgA antibody-secreting cells in salivary glands and IgA and IgG antibody-secreting cells in the superficial and central CLN; these responses were quantitatively enhanced if the antigen was coupled to CTB. Intraoral immunization also induced IgA and IgG antibody-secreting cells in the superficial and central CLN, but only if intact cholera toxin was included as an adjuvant. In contrast, subcutaneous (neck) immunization induced IgG antibody-secreting cells mainly in the draining facial lymph nodes. CLN cell populations resembled those of MLN, except that CLN lymphocytes had higher proportions of T cells and lower proportions of B cells and a slightly higher CD4+/CD8+ ratio among T cells than the MLN lymphocytes did. T cells that proliferated in response to antigen in vitro were found especially in central CLN 2 days after i.n. immunization and persisted for up to 6 months, whereas after intragastric immunization, responsive T cells were not found in the MLN for up to 14 days. After culture with antigen in vitro, T cells from the superficial CLN of i.n. immunized mice secreted both gamma interferon and interleukin-4. Therefore, after i.n. immunization, superficial and central CLN represent sites of regional lymphocyte development, and the central CLN in particular appear to be sites where memory T cells persist.
Wu
H Y
HY
Department of Microbiology, University of Alabama at Birmingham, 35294, USA.
Nikolova
E B
EB
Beagley
K W
KW
Eldridge
J H
JH
Russell
M W
MW
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001426:Bacterial Proteins; D002772:Cholera Toxin / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005145:Face; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009333:Neck; D009666:Nose / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D013270:Stomach / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C055764:S-layer proteins; D002772:Cholera Toxin