Efficient induction of T helper type 1-mediated immune responses in antigen-primed mice by anti-CD3 single-chain Fv/interleukin-18 fusion DNA.
Two types of T helper (Th) cells - Th1 and Th2 - play different roles in protection and immunopathology. The Th1 cell-mediated immune response plays an important role in inducing the host defence against intracellular bacteria and also in cancer immunotherapy. To effectively induce Th1 immune responses, we constructed a mammalian expression plasmid (pAnti-CD3sFv/IL-18) carrying a fusion gene in which anti-CD3 single-chain Fv (sFv) cDNA, the smallest unit of antibody recognizing the CD3 epsilon moiety of the T-cell receptor, was covalently linked to mature interleukin (IL)-18 cDNA. Intramuscular injection of ovalbumin (OVA)-sensitized BALB/c mice with pAnti-CD3sFv/IL-18 DNA efficiently increased the production of both OVA-specific interferon-gamma and anti-OVA immunoglobulin G2a, compared to injection with pAnti-CD3sFv DNA. In addition, pAnti-CD3sFv/IL-18 was more efficient than a mixture of pAnti-CD3sFv + pIL-18 in inducing OVA-specific, Th1 immune responses and also in inhibiting OVA-specific, IL-4 production. These studies indicate that vaccination with pAnti-CD3sFv/IL-18 fusion DNA efficiently induces the Th1 immune response in antigen-sensitized mice.
Kim
E J
EJ
Immunology Laboratory, College of Pharmacy, Chonnam National University, Kwangju, Korea.
Cho
D
D
Kim
T S
TS
D000485:Allergens / Q000494:pharmacology; D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016233:Immunotherapy, Active / Q000379:methods; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000235:genetics*; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D018417:Th1 Cells / Q000276:immunology*
D000485:Allergens; D017252:CD3 Complex; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D020382:Interleukin-18; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D004247:DNA