title: Oral immunization with the saliva-binding region of Streptococcus mutans AgI/II genetically coupled to the cholera toxin B subunit elicits T-helper-cell responses in gut-associated lymphoid tissues.
abstract: Mice immunized intragastrically (i.g.) with a genetically constructed chimeric protein consisting of the saliva-binding region (SBR) of Streptococcus mutans AgI/II coupled to cholera toxin (CT) A2 and B subunits (CTA2/B) develop serum immunoglobulin G (IgG) and mucosal IgA antibody responses against AgI/II that are enhanced by the coadministration of CT as an adjuvant. To investigate the development of antigen-specific T cells in the gut-associated lymphoid tissues, mice were immunized i.g. with SBR, SBR-CTA2/B, or SBR-CTA2/B plus CT. AgI/II-specific T cells in Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen were assayed by lymphoproliferation and flow cytometry for the expression of T-cell surface markers, and cytokine mRNA expression was evaluated by reverse transcription-PCR. T-cell responses were consistent with antibody responses but were detectable after the first immunization. Proliferative responses of PP and MLN cells upon stimulation with AgI/II in vitro were low and delayed in mice given SBR alone, and these cells displayed a mixed type 1 and 2 (or Th0) pattern of cytokine expression. Immunization with SBR-CTA2/B resulted in greater AgI/II-specific proliferative responses in PP cells and an increase in the proportion of CD4+ T cells. Coadministration of CT with SBR-CTA2/B led to greater proliferative responses especially in the MLN cells, which then showed an increase in CD4+ cells. Immunization with SBR-CTA2/B (with or without CT) skewed the cytokine expression pattern in PP and MLN cells toward Th2. The results indicate that T helper cells were induced in gut-associated lymphoid tissues by i.g. immunization with SBR-CTA2/B, concomitantly with and prior to the appearance of circulating and mucosal antibodies.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 35294, USA.
authors.forename: N
authors.initials: N
authors.lastname: Toida
authors.forename: G
authors.initials: G
authors.lastname: Hajishengallis
authors.forename: H Y
authors.initials: HY
authors.lastname: Wu
authors.forename: M W
authors.initials: MW
authors.lastname: Russell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007114:Immunization; D007422:Intestines / Q000276:immunology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D012463:Saliva / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D008562:Membrane Glycoproteins; C055764:S-layer proteins; D014614:Vaccines, Synthetic; D002772:Cholera Toxin