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1996-03-09
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).