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Porcine immunoregulatory cytokines

with special reference to their induction with CpG-containing DNA

Domeika, Kristina (2003). Porcine immunoregulatory cytokines. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae. Veterinaria, 1401-6257 ; 148
ISBN 91-576-6367-X
[Doctoral thesis]

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This thesis describes the possible adjuvant effects of bacterial DNA, in the form of a DNA vaccine plasmid (pcDNA3) or oligodeoxyribonucleotides (ODN), in the pig. The effects were assessed mainly as their ability to induce production of immunoregulatory cytokines. Furthermore, the cells producing type I or type II interferon (IFN) at various stimuli were studied. The plasmid pcDNA3 was shown to induce a local production of IFN-α in vivo, in subcutaneous tissue chambers. The in vivo effects of plasmids, expressing the cDNA for the cytokines GM-CSF or IL-6, were also tested. Such cytokine-expressing vectors could have adjuvant effects in DNA vaccines. The cDNA for porcine IL-12 (poIL-12) fusion protein was cloned into pcDNA3. The plasmid was shown to express poIL-12 with high in vitro biological activity in a bioassay. IL-12 and huIL-18 synergized in the induction of IFN-γ production in porcine peripheral blood mononuclear cells (poPBMC), and the IFN-γ producing cells were by flow cytometric analyses shown to be T-cells and NK cells. The antigen-presenting dendritic cells (DC) are important target cells in vaccination. Monocyte-derived dendritic cells (moDC) were differentiated from adherent monocytes in the presence of GM-CSF and IL-4 in vitro, and were able to produce different cytokines depending on stimuli. IL-12 was produced by the moDC mainly at stimulation with pcDNA3 (preincubated in lipofectin), Actinobacillus pleuropneumoniae and Sendai virus. IFN-α was only produced in response to Sendai virus, and IL-6 and IL-10 mainly in response to A. pleuropneumoniae. The presence of an unmethylated CpG dinucleotide in ODN was essential for the in vitro induction of IFN-α in poPBMC. The presence of a poly-guanine sequence in the ends of the ODN was shown to enhance its IFN-α inducing capacity. The IFN-α producing cells in response to CpG-ODN, lipofected pcDNA3 or Aujeszky’s disease virus were by flow cytometry and in situ hybridisation shown to be a rare cell population, resembling the human plasmacytoid DC, also referred to as natural IFN producing cells. The results show that certain forms of bacterial DNA have adjuvant effects in the pig, which could be of importance in the development of more efficient vaccines.

Authors/Creators:Domeika, Kristina
Title:Porcine immunoregulatory cytokines
Subtitle:with special reference to their induction with CpG-containing DNA
Series Name/Journal:Acta Universitatis Agriculturae Sueciae. Veterinaria
Year of publishing :February 2003
Number of Pages:53
ALLI. Johansson, E., Wallgren, P., Fuxler, L., Domeika K., Lefevre, F. & Fossum, C. 2002. The DNA vaccine vector pcDNA3 induces IFN-α production in pigs. Veterinary Immunology and Immunopathology 87, 29-40 II. Domeika, K., Berg, M., Eloranta, M-L. & Alm, G.V. 2002. Porcine interleukin-12 fusion protein and interleukin-18 in combination induce interferon-γ production in porcine natural killer and T cells. Veterinary Immunology and Immunopathology 86, 11-21 III. Johansson, E., Domeika, K., Berg, M., Alm, G.V. & Fossum, C. 2003. Characterisation of porcine monocyte-derived dendritic cells according to their cytokine profile. Veterinary Immunology and Immunopathology. In press IV. Domeika, K., Magnusson, M., Fuxler, L., Eloranta, M.-L., Alm, G.V. & Fossum, C. Characteristics of oligodeoxyribonucleotides that induce interferon-α production in infrequent porcine blood leukocytes. Manuscript.
Place of Publication:Uppsala
ISBN for printed version:91-576-6367-X
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L70 Veterinary science and hygiene - General aspects
Subjects:Not in use, please see Agris categories
Agrovoc terms:swine, vaccines, adjuvants, cytokines, interferons, plasmids, interleukins, in vitro
Keywords:CpG-DNA, cytokines, dendritic cells, DNA vaccines, interferon-γ, interleukin-12, interleukin-18, porcine, type I interferon
Permanent URL:
ID Code:133
Department:(VH) > Institutionen för veterinärmedicinsk mikrobiologi
Deposited By: Kristina Domeika
Deposited On:10 Feb 2003 00:00
Metadata Last Modified:02 Dec 2014 10:01

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