TY - JOUR
T1 - Induction of Th2-directed immune responses by IL-4-transduced dendritic cells in mice
AU - Hayashi, Satoru
AU - Johnston, Stephen A.
AU - Takashima, Akira
N1 - Funding Information:
We thank Drs. Paul R. Bergstresser and Shinji Shimada for critical suggestions and Pat Adcock for her excellent secretarial assistance in preparing this manuscript. This study was supported by NIH grants (RO1-AR35068, RO1-AR43777, and RO1-AI43262 to A.T.), sponsored research agreement (S.A.J and A.T.) from GeneMedicine Inc., and CE.R.I.E.S. Award (A.T.).
PY - 2000/7/15
Y1 - 2000/7/15
N2 - Dendritic cell (DC)-based vaccines have been used to generate Th1-mediated, protective immunity against cancers and infectious microorganisms. As an attempt to develop a new vaccine protocol for the induction of Th2-directed responses, we introduced an IL-4 plasmid vector into the XS106 DC line (derived from A/J mice). Although relatively small fractions of XS106 cells exhibited apparent intracellular deposition of IL-4, they secreted biologically relevant amounts of the cytokine. IL-4-transduced XS106 DC and control XS106 DC transfected with vector alone were pulsed with KLH and injected s.c. into A/J mice. The overall magnitude of KLH-specific cellular and humoral responses was comparable between the two animal groups. However, they differed in the isotype profile albeit only transiently, with the IL-4-transduced DC group showing higher IgE and lower IgG2a responses, and in the cytokine profile, with spleen cells isolated from the IL-4-transduced DC group producing higher IL-13 and lower IL-12. Thus, delivery of IL-4 gene to relatively small numbers of DC is sufficient to modify the immunological outcome of DC-based vaccines. Copyright (C) 2000 Elsevier Science Ltd.
AB - Dendritic cell (DC)-based vaccines have been used to generate Th1-mediated, protective immunity against cancers and infectious microorganisms. As an attempt to develop a new vaccine protocol for the induction of Th2-directed responses, we introduced an IL-4 plasmid vector into the XS106 DC line (derived from A/J mice). Although relatively small fractions of XS106 cells exhibited apparent intracellular deposition of IL-4, they secreted biologically relevant amounts of the cytokine. IL-4-transduced XS106 DC and control XS106 DC transfected with vector alone were pulsed with KLH and injected s.c. into A/J mice. The overall magnitude of KLH-specific cellular and humoral responses was comparable between the two animal groups. However, they differed in the isotype profile albeit only transiently, with the IL-4-transduced DC group showing higher IgE and lower IgG2a responses, and in the cytokine profile, with spleen cells isolated from the IL-4-transduced DC group producing higher IL-13 and lower IL-12. Thus, delivery of IL-4 gene to relatively small numbers of DC is sufficient to modify the immunological outcome of DC-based vaccines. Copyright (C) 2000 Elsevier Science Ltd.
KW - Dendritic cells
KW - IL-4
KW - Th2-biased immune responses
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U2 - 10.1016/S0264-410X(00)00140-7
DO - 10.1016/S0264-410X(00)00140-7
M3 - Article
C2 - 10856789
AN - SCOPUS:0034662448
SN - 0264-410X
VL - 18
SP - 3097
EP - 3105
JO - Vaccine
JF - Vaccine
IS - 27
ER -