title: Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.
abstract: We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2-type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2 as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+ CD4- cells revealed that only the latter cell population had consistently elevated IL-6 gene expression, whereas both sorted populations exhibited increased IFN-gamma and IL-10 gene expression. Thus, orally administered recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in both mucosal and systemic tissues. Macrophages producing IL-6 were also evident. Our results are consistent with the suggestion that Ag-specific Th1 cells and their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with IL-6 produced by macrophages provide important signals for the development of mucosal IgA and serum IgG subclass responses in the absence of preferential expression of Th2 cytokines IL-4 and IL-5.
authors.affiliation: Immunobiology Vaccine Center, University of Alabama Medical Center, Birmingham 35294, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: VanCott
authors.forename: H F
authors.initials: HF
authors.lastname: Staats
authors.forename: D W
authors.initials: DW
authors.lastname: Pascual
authors.forename: M
authors.initials: M
authors.lastname: Roberts
authors.forename: S N
authors.initials: SN
authors.lastname: Chatfield
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Coste
authors.forename: P B
authors.initials: PB
authors.lastname: Carter
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012486:Salmonella typhimurium / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D001428:Bacterial Vaccines; D016207:Cytokines; D015850:Interleukin-6; D014614:Vaccines, Synthetic; D016753:Interleukin-10