J Korean Med Sci.  2004 Oct;19(5):640-646. 10.3346/jkms.2004.19.5.640.

Effects of Cytokine Milieu Secreted by BCG-treated Dendritic Cells on Allergen-Specific Th Immune Response

Affiliations
  • 1Department of Allergy and Hematology, Chonnam National University Medical School and Research Institute of Medical Science, Gwangju, Korea. yikoh@chonnam.ac.kr

Abstract

Bacillus Calmette-Guerin (BCG) is reported to suppress Th2 response and asthmatic reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections with BCG are known to result in inducing various cytokines. Thus, DCs are likely to play a role in the effects of BCG on asthma. This study aims at investigating that cytokine milieu secreted by BCG-treated DCs directly enhances allergen-specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics. DCs were cultured with and without BCG and subjected to flow cytometric analysis. IL-12 and IL-10 were determined from the culture supernatants. Some DCs were cocultured with T cells in the presence of D. farinae extracts after adding the culture supernatants from BCG-treated DCs, and IL-5 and IFN-gamma were determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86, and CD40, and the productions of IL-12 and IL-10. Addition of culture supernatants from BCG-treated DCs up-regulated production of IFN-gamma by T cells stimulated by DCs and D. farinae extracts (p<0.05), but did not down-regulate production of IL-5 (p>0.05). The cytokine milieu secreted by BCG-treated DCs directly enhanced allergen-specific Th1 response, although did not suppress Th2 response.

Keyword

Asthma; Cytokines; Dendritic Cells; Mycobacterium bovis; T-lymphocytes

MeSH Terms

Antigens, Dermatophagoides/*immunology
Asthma/*immunology
Cells, Cultured
Coculture Techniques
Culture Media
Cytokines/*immunology/secretion
Dendritic Cells/cytology/*immunology/secretion
Humans
Hypersensitivity/immunology
Interferon Type II/immunology/secretion
Interleukin-10/immunology/secretion
Interleukin-12/immunology/secretion
Interleukin-5/immunology/secretion
Lymphocyte Activation/immunology
Mycobacterium bovis/*immunology
Research Support, Non-U.S. Gov't
Th2 Cells/cytology/immunology/secretion
Up-Regulation/immunology

Figure

  • Fig. 1 Comparisons of surface antigen expression between untreated DCs and BCG-treated DCs from asthmatics. Expression represents the percentage of positive cells on FACS analysis after staining with the corresponding antibodies. Data are expressed mean±SEM. Statistical significance was determined by using the Wilcoxon's signed-rank test.

  • Fig. 2 Comparisons of IL-12 (A) and IL-10 (B) productions between untreated DCs and BCG-treated DCs from asthmatics. Statistical significance was determined by using the Wilcoxon's signed-rank test.

  • Fig. 3 Comparisons of T cell proliferations among T cell alone (T), T-DC coculture (T/DC), T-DC coculture in the presence of D. farinae extracts (T/DC/Df), and T-DC coculture in the presence of D. farinae extracts after adding the culture supernatant from BCG-treated DC (T/DC/Df/Supernatant) in D. farinae-sensitive asthmatics. Statistical significance was determined by using the Wilcoxon's signed-rank test.

  • Fig. 4 Comparisons of IFN-γ (A) and IL-5 (B) productions by T cells from D. farinae-sensitive asthmatics between T-DC coculture in the presence of D. farinae extracts (T/DC/Df) and T-DC coculture in the presence of D. farinae extracts after adding the culture supernatant from BCG-treated DC (T/DC/Df/Supernatant). Statistical significance was determined by using the Wilcoxon's signed-rank test.


Cited by  1 articles

BCG-Induced Dendritic Cell Responses and Suppression of Interleukin-5 Production from T Cells in Atopic Asthmatics
Inseon S. Choi, Xiang-Hua Lin, Young-Ah Koh, Yong Cui
J Korean Med Sci. 2008;23(4):628-634.    doi: 10.3346/jkms.2008.23.4.628.


Reference

1. Romagnani S. Regulation of the development of type 2 T-helper cells in allergy. Curr Opin Immunol. 1994. 6:838–846.
Article
2. Mocci S, Coffman RL. Induction of a Th2 population from a polarized Leishmania-specific Th1 population by in vitro culture with IL-4. J Immunol. 1995. 154:3779–3787.
3. Holt PG. A potential vaccine strategy for asthma and allied atopic diseases during early childhood. Lancet. 1994. 344:456–458.
Article
4. Del Prete GF, De Carli M, Mastromauro C, Biagiotti R, Macchia D, Falagiani P, Ricci M, Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991. 88:346–350.
Article
5. Kemp EB, Belshe RB, Hoft DF. Immune responses stimulated by percutaneous and intradermal bacille Calmette-Guerin. J Infect Dis. 1996. 174:113–119.
Article
6. Koh YI, Choi IS, Kim WY. BCG infection in allergen-presensitized rats suppresses Th2 immune response and prevents the development of allergic asthmatic reaction. J Clin Immunol. 2001. 21:51–59.
7. Koh YI, Choi IS, Park SC, Kang KW. BCG infection during presensitization or even post-sensitization inhibits airway sensitivity in an animal model of allergic asthma. J Korean Med Sci. 2000. 15:265–272.
Article
8. Choi IS, Koh YI. Therapeutic effects of BCG vaccination in adult asthmatic patients: a randomized, controlled trial. Ann Allergy Asthma Immunol. 2002. 88:584–591.
Article
9. Choi IS, Koh YI. Effects of BCG revaccination on asthma. Allergy. 2003. 58:1114–1116.
Article
10. Jiao X, Lo-Man R, Guermonprez P, Fiette L, Deriaud E, Burgaud S, Gicquel B, Winter N, Leclerc C. Dendritic cells are host cells for mycobacteria in vivo that trigger innate and acquired immunity. J Immunol. 2002. 168:1294–1301.
Article
11. Henderson RA, Watkins SC, Flynn JL. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J Immunol. 1997. 159:635–643.
12. Kim KD, Lee HG, Kim JK, Park SN, Choe IS, Choe YK, Kim SJ, Lee E, Lim JS. Enhanced antigen-presenting activity and tumour necrosis factor-alpha-independent activation of dendritic cells following treatment with Mycobacterium bovis bacillus Calmette-Guerin. Immunology. 1999. 97:626–633.
13. O'Donnell MA, Luo Y, Chen X, Szilvasi A, Hunter SE, Clinton SK. Role of IL-12 in the induction and potentiation of IFN-gamma in response to bacillus Calmette-Guerin. J Immunol. 1999. 163:4246–4252.
14. Giacomini E, Iona E, Ferroni L, Miettinen M, Fattorini L, Orefici G, Julkunen I, Coccia EM. Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response. J Immunol. 2001. 166:7033–7041.
15. Buelens C, Verhasselt V, De Groote D, Thielemans K, Goldman M, Willems F. Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10. Eur J Immunol. 1997. 27:1848–1852.
Article
16. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis. 1987. 136:225–244.
17. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998. 392:245–252.
Article
18. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 1993. 177:1199–1204.
Article
19. Sareneva T, Julkunen I, Matikainen S. IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells. J Immunol. 2000. 165:1933–1938.
20. Lack G, Bradley KL, Hamelmann E, Renz H, Loader J, Leung DY, Larsen G, Gelfand EW. Nebulized IFN-gamma inhibits the development of secondary allergic responses in mice. J Immunol. 1996. 157:1432–1439.
21. Marshall JD, Secrist H, DeKruyff RH, Wolf SF, Umetsu DT. IL-12 inhibits the production of IL-4 and IL-10 in allergen-specific human CD4+ T lymphocytes. J Immunol. 1995. 155:111–117.
22. Swain SL. Generation and in vivo persistence of polarized Th1 and Th2 memory cells. Immunity. 1994. 1:543–552.
Article
23. Guler ML, Gorham JD, Hsieh CS, Mackey AJ, Steen RG, Dietrich WF, Murphy KM. Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development. Science. 1996. 271:984–987.
Article
24. De Wit D, Amraoui Z, Vincart B, Michel O, Michils A, Van Overvelt L, Willems F, Goldman M. Helper T-cell responses elicited by Der p 1-pulsed dendritic cells and recombinant IL-12 in atopic and healthy subjects. J Allergy Clin Immunol. 2000. 105:346–352.
Article
25. Arkwright PD, David TJ. Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. J Allergy Clin Immunol. 2001. 107:531–534.
Article
26. Barnes PJ, Liew FY. Nitric oxide and asthmatic inflammation. Immunol Today. 1995. 16:128–130.
Article
27. Hogman M, Frostell CG, Hedenstrom H, Hedenstierna G. Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis. 1993. 148:1474–1478.
Article
28. Nijkamp FP, van der Linde HJ, Folkerts G. Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. Am Rev Respir Dis. 1993. 148:727–734.
29. Hofstra CL, Van Ark I, Hofman G, Nijkamp FP, Jardieu PM, Van Oosterhout AJ. Differential effects of endogenous and exogenous interferon-gamma on immunoglobulin E, cellular infiltration, and airway responsiveness in a murine model of allergic asthma. Am J Respir Cell Mol Biol. 1998. 19:826–835.
30. Koh YI, Choi IS, Lee HC. Relationship between changes in interferon-gamma production by peripheral blood T cells and changes in peak expiratory flow rate in patients with chronic stable asthma. Clin Exp Allergy. 2002. 32:1734–1738.
31. Pretolani M, Goldman M. IL-10: a potential therapy for allergic inflammation? Immunol Today. 1997. 18:277–280.
Article
32. Zuany-Amorim C, Sawicka E, Manlius C, Le Moine A, Brunet LR, Kemeny DM, Bowen G, Rook G, Walker C. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med. 2002. 8:625–629.
Article
33. Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol. 2001. 2:725–731.
Article
34. Bellinghausen I, Brand U, Knop J, Saloga J. Comparison of allergen-stimulated dendritic cells from atopic and nonatopic donors dissecting their effect on autologous naive and memory T helper cells of such donors. J Allergy Clin Immunol. 2000. 105:988–996.
Article
35. Joss A, Akdis M, Faith A, Blaser K, Akdis CA. IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol. 2000. 30:1683–1690.
Article
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