Regulation of cytokine production by sugi allergen-pullulan conjugate.
Sugi basic protein (SBP), a major allergen of Japanese cedar (Cryptomeria japonica) pollen, conjugated to pullulan (alpha-1,4'-, alpha-1,6'-glucan) reportedly suppresses IgE anti-SBP antibody production and enhances IgG anti-SBP antibody production in mice. We analyzed cytokine production by SBP-specific T cells after stimulation with an SBP-pullulan conjugate (SBP-P), native SBP, or a mixture of SBP and pullulan. When SBP-specific T cell lines were stimulated with the SBP-P conjugate in the presence of antigen-presenting cells (APC), the production of IFN-gamma, IL-4, IL-5, and IL-10 decreased compared with the cytokine levels produced by SBP-stimulated T cells. However, when these T cells were repeatedly stimulated with the SBP-P conjugate, the production of IFN-gamma increased progressively, while that of IL-4, IL-5, and IL-10 remained decreased compared with the T cells that were repeatedly stimulated with native SBP. Stimulation of the T cells with the mixture of SBP and pullulan showed little difference in the cytokine production profile from that observed after stimulation with native SBP alone. Interestingly, when the T cell lines stimulated repeatedly with SBP-P were subsequently stimulated with native SBP, a further increase in IFN-gamma production was observed, while IL-10 production decreased. Inhibition of IL-4 production was also observed when SBP-specific Th2 clones were stimulated with SBP-P. These results indicate that stimulation of T cells with SBP-P up-regulates Th1 cytokine production, while down-regulating that of Th2. It is, therefore, conceivable that immunotherapeutic treatment with the SBP-P conjugate rather than with conventional SBP solutions is preferable for improving Japanese cedar pollen allergy.
Kohno
K
K
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Ohtsuki
T
T
Suemoto
Y
Y
Inoue
T
T
Taniguchi
Y
Y
Usui
M
M
Ikeda
M
M
Kurimoto
M
M
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D052179:Antigens, Plant; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005936:Glucans / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000494:pharmacology*; D011058:Pollen; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; D005936:Glucans; D007155:Immunologic Factors; D007375:Interleukin-1; D007378:Interleukins; D008222:Lymphokines; D010940:Plant Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; C009109:pullulan