Journal of Nanoparticle Research

, Volume 13, Issue 6, pp 2577–2585 | Cite as

Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

  • Lanxia Liu
  • Yuanyuan Bai
  • Dunwan Zhu
  • Liping Song
  • Hai Wang
  • Xia Dong
  • Hailing Zhang
  • Xigang Leng
Research Paper
  • 105 Downloads

Abstract

Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells. The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells. It was also demonstrated that, when directly exposed to the naive CD4+ T cells, the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4+ T cell polarization, nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines.

Keywords

Chitosan Nanoparticle Gene delivery Naive CD4+ T cell Nanomedicine 

Notes

Acknowledgments

This research was jointly supported by the Ministry of Science and Technology of China (Grant No: 2005DIB1J094, 2006CB933203) and the National Natural Science Foundation of China (Grant No: 90406024).

References

  1. Bivas-Benita M, van Meijgaarden KE, Franken KL et al (2004) Pulmonary delivery of chitosan–DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis. Vaccine 22:1609–1615CrossRefGoogle Scholar
  2. Bloomfield VA (1996) DNA condensation. Curr Opin Struct Biol 6:334–341CrossRefGoogle Scholar
  3. Castignolles N, Morgeaux S, Gontier-Jallet C et al (1996) A new family of carriers (biovectors) enhances the immunogenicity of rabies antigens. Vaccine 14:1353–1360CrossRefGoogle Scholar
  4. Chellat F, Grandjean-Laquerriere A, Le Naour R et al (2005) Metalloproteinase and cytokine production by THP-1 macrophages following exposure to chitosan–DNA nanoparticles. Biomaterials 26:961–970CrossRefGoogle Scholar
  5. Chen YW, Hwang KC, Yen CC et al (2004) Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am J Physiol Regul Integr Comp Physiol 287:R21–R26CrossRefGoogle Scholar
  6. Cong YP, Song SS, Bhagat L et al (2003) Self-stabilized CpG DNAs optimally activate human B cells and plasmacytoid dendritic cells. Biochem Biophys Res Commun 310:1133–1139CrossRefGoogle Scholar
  7. De Jong WH (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomed 3:133–149CrossRefGoogle Scholar
  8. Dianzani C, Cavalli R, Zara GP et al (2006) Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells. Br J Pharmacol 148:648–656CrossRefGoogle Scholar
  9. Dykman LA, Sumaroka MV, Staroverov SA et al (2004) Immunogenic properties of the colloidal gold. Izv Akad Nauk Ser Biol 1:86–91Google Scholar
  10. Feili-Hariri M, Falkner DH, Morel PA (2005) Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy. J Leukoc Biol 78:656–664CrossRefGoogle Scholar
  11. Gioannini TL, Teghanemt A, Zhang D et al (2004) Isolation of an endotoxin-MD-2 complex that produces toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc Natl Acad Sci USA 101:4186–4191CrossRefGoogle Scholar
  12. Higaki M, Ishihara T, Izumo N et al (2005) Treatment of experimental arthritis with poly(d, l-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate. Ann Rheum Dis 64:1132–1136CrossRefGoogle Scholar
  13. Kemp TJ, Elzey BD, Griffith TS (2003) Plasmacytoid dendritic cell-derived IFN-alpha induces TNF-related apoptosis-inducing ligand/Apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation. J Immunol 171:212–218Google Scholar
  14. Koch A, Knobloch J, Dammhayn C et al (2007) Effect of bacterial endotoxin LPS on expression of INF-gamma and IL-5 in T-lymphocytes from asthmatics. Clin Immunol 125:194–204CrossRefGoogle Scholar
  15. Li F, Wang L, Jin XM et al (2009) The immunologic effect of TGF-beta1 chitosan nanoparticle plasmids on ovalbumin-induced allergic BALB/c mice. Immunobiology 214:87–99CrossRefGoogle Scholar
  16. Liu L, Song C, Song L et al (2009) Effects of alkylated-chitosan CDNA nanoparticles on the function of macrophages. J Mater Sci Mater Med 20:943–948CrossRefGoogle Scholar
  17. MacLaughlin FC, Mumper RJ, Wang J et al (1998) Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery. J Control Release 56:259–272CrossRefGoogle Scholar
  18. Mao HQ, Roy K, Troung-Le VL et al (2001) Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release 70:399–421CrossRefGoogle Scholar
  19. Marcinkiewicz J, Polewska A, Knapczyk J (1991) Immunoadjuvant properties of chitosan. Arch Immunol Ther Exp (Warsz) 39:127–132Google Scholar
  20. Meng Z, Shao J, Xiang L (2003) CpG oligodeoxynucleotides activate grass carp (Ctenopharyngodon idellus) macrophages. Dev Comp Immunol 27:313–321CrossRefGoogle Scholar
  21. Mukherjee S, Chen LY, Papadimos TJ et al (2009) Lipopolysaccharide-driven Th2 cytokine production in macrophages is regulated by both MyD88 and TRAM. J Biol Chem 284:29391–29398CrossRefGoogle Scholar
  22. Nishimura K, Nishimura S, Nishi N et al (1985) Adjuvant activity of chitin derivatives in mice and guinea-pigs. Vaccine 3:379–384CrossRefGoogle Scholar
  23. Obminska-Mrukowicz B, Szczypka M, Gaweda B (2006) Modulatory effects of chitosan adipate on the T and B lymphocyte subsets in mice. J Vet Sci 7:157–160Google Scholar
  24. Pouliot P, Turmel V, Gelinas E et al (2005) Interleukin-4 production by human alveolar macrophages. Clin Exp Allergy 35:804–810CrossRefGoogle Scholar
  25. Richardson SC, Kolbe HV, Duncan R (1999) Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA. Int J Pharm 178:231–243CrossRefGoogle Scholar
  26. Seferian PG, Martinez ML (2000) Immune stimulating activity of two new chitosan containing adjuvant formulations. Vaccine 19:661–668CrossRefGoogle Scholar
  27. Shaunak S, Thomas S, Gianasi E et al (2004) Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Nat Biotechnol 22:977–984CrossRefGoogle Scholar
  28. van der Lubben IM, Kersten G, Fretz MM et al (2003) Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine 21:1400–1408CrossRefGoogle Scholar
  29. Watford WT, Moriguchi M, Morinobu A et al (2003) The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev 14:361–368CrossRefGoogle Scholar
  30. Westerink MA, Smithson SL, Srivastava N et al (2001) ProJuvant (Pluronic F127/chitosan) enhances the immune response to intranasally administered tetanus toxoid. Vaccine 20:711–723CrossRefGoogle Scholar
  31. Zenewicz LA, Antov A, Flavell RA (2009) CD4 T-cell differentiation and inflammatory bowel disease. Trends Mol Med 15:199–207CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Lanxia Liu
    • 1
  • Yuanyuan Bai
    • 1
  • Dunwan Zhu
    • 1
  • Liping Song
    • 1
  • Hai Wang
    • 1
  • Xia Dong
    • 1
  • Hailing Zhang
    • 1
  • Xigang Leng
    • 1
  1. 1.Lab of Bioengineering, Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical MaterialsTianjinPeople’s Republic of China

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