Document 0136
 DOCN  M9650136
 TI    Regulation of mucosal and systemic antibody responses by T helper cell
       subsets, macrophages, and derived cytokines following oral immunization
       with live recombinant Salmonella.
 DT    9605
 AU    VanCott JL; Staats HF; Pascual DW; Roberts M; Chatfield SN; Yamamoto M;
       Coste M; Carter PB; Kiyono H; McGhee JR; Immunobiology Vaccine Center,
       University of Alabama Medical; Center, Birmingham 35294, USA.
 SO    J Immunol. 1996 Feb 15;156(4):1504-14. Unique Identifier : AIDSLINE
       MED/96164580
 AB    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.
 DE    Administration, Oral  Animal  Bacterial Vaccines/IMMUNOLOGY
       Cytokines/*IMMUNOLOGY  Hypersensitivity, Delayed/IMMUNOLOGY  *Immunity,
       Mucosal  Interleukin-10/BIOSYNTHESIS  Interleukin-6/METABOLISM
       Macrophages/*IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred C57BL
       Salmonella typhimurium/*IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       T-Lymphocyte Subsets/*IMMUNOLOGY  T-Lymphocytes,
       Helper-Inducer/*IMMUNOLOGY  Th1 Cells/IMMUNOLOGY  Vaccines, Synthetic
       JOURNAL ARTICLE

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