Skip to main content
Erschienen in: Journal of Clinical Immunology 2/2010

01.03.2010

CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice

verfasst von: Cyro A. de Brito, Ana E. Fusaro, Jefferson R. Victor, Paula O. Rigato, Adriana L. Goldoni, Bruno P. Muniz, Alberto J. S. Duarte, Maria N. Sato

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization.

Objective

The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice.

Results and Discussion

Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-γ upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG.

Conclusion

Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.
Literatur
1.
Zurück zum Zitat Björkstén B. The intrauterine and postnatal environments. J Allergy Clin Immunol. 1999;104:1119–27.CrossRefPubMed Björkstén B. The intrauterine and postnatal environments. J Allergy Clin Immunol. 1999;104:1119–27.CrossRefPubMed
2.
Zurück zum Zitat Pawankar R, Baena-Cagnani CE, Bousquet J, Canonica GW, Cruz AA, Kaliner MA, et al. State of World Allergy Report 2008: allergy and chronic respiratory diseases. WAO J Suppl. 2008;1:S4–17. Pawankar R, Baena-Cagnani CE, Bousquet J, Canonica GW, Cruz AA, Kaliner MA, et al. State of World Allergy Report 2008: allergy and chronic respiratory diseases. WAO J Suppl. 2008;1:S4–17.
3.
Zurück zum Zitat Adkins B, Du RQ. Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are biased to Th2 secondary responses. J Immunol. 1998;160:4217–24.PubMed Adkins B, Du RQ. Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are biased to Th2 secondary responses. J Immunol. 1998;160:4217–24.PubMed
4.
Zurück zum Zitat Li L, Lee HH, Bell JJ, Gregg RK, Sellis JS, Gessner A, et al. IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2. Immunity. 2004;20:429–40.CrossRefPubMed Li L, Lee HH, Bell JJ, Gregg RK, Sellis JS, Gessner A, et al. IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2. Immunity. 2004;20:429–40.CrossRefPubMed
5.
Zurück zum Zitat Rose S, Lichtenheld M, Foote MR, Adkins B. Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. J Immunol. 2007;178:2667–78.PubMed Rose S, Lichtenheld M, Foote MR, Adkins B. Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. J Immunol. 2007;178:2667–78.PubMed
6.
Zurück zum Zitat Forsthuber T, Yip HC, Lehmann PV. Induction of Th1 and Th2 immunity in neonatal mice. Science. 1996;217:1728–30.CrossRef Forsthuber T, Yip HC, Lehmann PV. Induction of Th1 and Th2 immunity in neonatal mice. Science. 1996;217:1728–30.CrossRef
7.
Zurück zum Zitat Jupelli M, Guentzel MN, Meier PA, Zhong G, Murthy AK, Arulanandam BP. Endogenous IFN-γ production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice. J Immunol. 2008;180:4148–55.PubMed Jupelli M, Guentzel MN, Meier PA, Zhong G, Murthy AK, Arulanandam BP. Endogenous IFN-γ production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice. J Immunol. 2008;180:4148–55.PubMed
8.
Zurück zum Zitat Shen H, Huang H, Wang J, Ye S, Li W, Wang K, et al. Neonatal vaccination with Bacillus Calmette-Guérin elicits long-term protection in mouse-allergic responses. Allergy. 2008;63:555–63.CrossRefPubMed Shen H, Huang H, Wang J, Ye S, Li W, Wang K, et al. Neonatal vaccination with Bacillus Calmette-Guérin elicits long-term protection in mouse-allergic responses. Allergy. 2008;63:555–63.CrossRefPubMed
9.
Zurück zum Zitat Kline JN, Waldschmidt TJ, Businga TR, Lemish JE, Weinstock JV, Thorne PS, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol. 1998;160:2555–9.PubMed Kline JN, Waldschmidt TJ, Businga TR, Lemish JE, Weinstock JV, Thorne PS, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol. 1998;160:2555–9.PubMed
10.
Zurück zum Zitat Horner AA, Takabayashi K, Beck L, et al. Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity. J Allergy Clin Immunol. 2002;110:413–20.CrossRefPubMed Horner AA, Takabayashi K, Beck L, et al. Optimized conjugation ratios lead to allergen immunostimulatory oligodeoxynucleotide conjugates with retained immunogenicity and minimal anaphylactogenicity. J Allergy Clin Immunol. 2002;110:413–20.CrossRefPubMed
11.
Zurück zum Zitat Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–5.CrossRefPubMed Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–5.CrossRefPubMed
12.
Zurück zum Zitat Bauer S, Wagner H. Bacterial CpG-DNA licenses TLR9. Curr Top Microbiol Immunol. 2002;270:145–54.PubMed Bauer S, Wagner H. Bacterial CpG-DNA licenses TLR9. Curr Top Microbiol Immunol. 2002;270:145–54.PubMed
13.
Zurück zum Zitat Stacey KJ, Sweet MJ, Hume DA. Macrophages ingest and are activated by bacterial DNA. J Immunol. 1996;157:2116–22.PubMed Stacey KJ, Sweet MJ, Hume DA. Macrophages ingest and are activated by bacterial DNA. J Immunol. 1996;157:2116–22.PubMed
14.
Zurück zum Zitat Wild JS, Sur S. CpG oligonucleotide modulation of allergic inflammation. Eur J Allergy Clin Immunol. 2001;56:365–76.CrossRef Wild JS, Sur S. CpG oligonucleotide modulation of allergic inflammation. Eur J Allergy Clin Immunol. 2001;56:365–76.CrossRef
15.
Zurück zum Zitat Lin L, Gerth AJ, Peng SL. CpG DNA redirects class-switching towards “Th1-like” Ig isotype production via TLR9 and MyD88. Eur J Immunol. 2004;34:1483–7.CrossRefPubMed Lin L, Gerth AJ, Peng SL. CpG DNA redirects class-switching towards “Th1-like” Ig isotype production via TLR9 and MyD88. Eur J Immunol. 2004;34:1483–7.CrossRefPubMed
16.
Zurück zum Zitat Liu N, Ohnishi N, Ni L, Akira S, Bacon KB. CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nature Immunol. 2003;4:687–93.CrossRef Liu N, Ohnishi N, Ni L, Akira S, Bacon KB. CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nature Immunol. 2003;4:687–93.CrossRef
17.
Zurück zum Zitat Brazolot Millan CL, Weeratna R, Krieg AM, Siegrist C-A, Davis HL. CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc Natl Acad Sci U S A. 1998;95:15553–8.CrossRefPubMed Brazolot Millan CL, Weeratna R, Krieg AM, Siegrist C-A, Davis HL. CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc Natl Acad Sci U S A. 1998;95:15553–8.CrossRefPubMed
18.
Zurück zum Zitat Kovarik J, Bozzotti P, Love-Homan L, Pihlgren M, Davis HL, Lambert PH, et al. CpG oligodeoxynucleotides can circumvent the Th2 polarization of neonatal responses to vaccines but may fail to fully redirect Th2 responses established by neonatal priming. J Immunol. 1999;162:1611–17.PubMed Kovarik J, Bozzotti P, Love-Homan L, Pihlgren M, Davis HL, Lambert PH, et al. CpG oligodeoxynucleotides can circumvent the Th2 polarization of neonatal responses to vaccines but may fail to fully redirect Th2 responses established by neonatal priming. J Immunol. 1999;162:1611–17.PubMed
19.
Zurück zum Zitat Jegerlehner A, Maurer P, Bessa J, Hinton HJ, Kopf M, Bachmann MF. TLR9 signaling in B cells determines class switch recombination to IgG2a. J Immunol. 2007;178:2415–20.PubMed Jegerlehner A, Maurer P, Bessa J, Hinton HJ, Kopf M, Bachmann MF. TLR9 signaling in B cells determines class switch recombination to IgG2a. J Immunol. 2007;178:2415–20.PubMed
20.
Zurück zum Zitat Tasker L, Marshall-Clarke S. Functional responses of human neonatal B lymphocytes to antigen cross-linking and CpG DNA. Clin Exp Immunol. 2003;134:409–19.CrossRefPubMed Tasker L, Marshall-Clarke S. Functional responses of human neonatal B lymphocytes to antigen cross-linking and CpG DNA. Clin Exp Immunol. 2003;134:409–19.CrossRefPubMed
21.
Zurück zum Zitat De Wit D, Olislagers V, Goriely S, Vermeulen F, Wagner H, Goldman M, et al. Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns. Blood. 2004;103:1030–2.CrossRefPubMed De Wit D, Olislagers V, Goriely S, Vermeulen F, Wagner H, Goldman M, et al. Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns. Blood. 2004;103:1030–2.CrossRefPubMed
22.
Zurück zum Zitat Oliveira CR, Taniguchi EA, Fusaro AE, Victor JR, Brito CA, Duarte AJS, et al. Bystander effect in synergy to anergy in oral tolerance of Blomia tropicalis/ovalbumin murine co-immunization model. J Clin Immunol. 2005;25:153–61.CrossRefPubMed Oliveira CR, Taniguchi EA, Fusaro AE, Victor JR, Brito CA, Duarte AJS, et al. Bystander effect in synergy to anergy in oral tolerance of Blomia tropicalis/ovalbumin murine co-immunization model. J Clin Immunol. 2005;25:153–61.CrossRefPubMed
23.
Zurück zum Zitat Mota I, Wong D. Homologous and heterologous passive cutaneous anaphylactic activity of mouse antisera during the course of immunization. Life Sci. 1969;8:813–20.CrossRefPubMed Mota I, Wong D. Homologous and heterologous passive cutaneous anaphylactic activity of mouse antisera during the course of immunization. Life Sci. 1969;8:813–20.CrossRefPubMed
24.
Zurück zum Zitat Ovary Z. Passive cutaneous anaphylaxis in the mouse. J Immunol. 1958;81:355–7.PubMed Ovary Z. Passive cutaneous anaphylaxis in the mouse. J Immunol. 1958;81:355–7.PubMed
25.
Zurück zum Zitat Fusaro AE, Brito CA, Victor JR, Rigato PO, Goldoni AL, Duarte AJS, et al. Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding. Immunology. 2007;122:107–15.CrossRefPubMed Fusaro AE, Brito CA, Victor JR, Rigato PO, Goldoni AL, Duarte AJS, et al. Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding. Immunology. 2007;122:107–15.CrossRefPubMed
26.
Zurück zum Zitat Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol. 2004;4:553–64.CrossRefPubMed Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol. 2004;4:553–64.CrossRefPubMed
27.
Zurück zum Zitat Faquim-Mauro EL, Coffman RL, Abrahamsohn IA, Macedo MS. Mouse IgG1 antibodies comprise two functionally distinct types that are differentially regulated by IL-4 and IL-12. J Immunol. 1999;163:3572–6.PubMed Faquim-Mauro EL, Coffman RL, Abrahamsohn IA, Macedo MS. Mouse IgG1 antibodies comprise two functionally distinct types that are differentially regulated by IL-4 and IL-12. J Immunol. 1999;163:3572–6.PubMed
28.
Zurück zum Zitat Bourke E, Bosisio D, Golay J, Polentarutti N, Mantovani A. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood. 2003;102:956–63.CrossRefPubMed Bourke E, Bosisio D, Golay J, Polentarutti N, Mantovani A. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood. 2003;102:956–63.CrossRefPubMed
29.
Zurück zum Zitat Bernasconi NL, Onai N, Lanzavecchia A. A role for toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood. 2003;101:4500–4.CrossRefPubMed Bernasconi NL, Onai N, Lanzavecchia A. A role for toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood. 2003;101:4500–4.CrossRefPubMed
30.
Zurück zum Zitat Taylor PA, Lees CJ, Fournier S, Allison JP, Sharpe AH, Blazar BR. B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via R–T interactions. J Immunol. 2004;172:34–9.PubMed Taylor PA, Lees CJ, Fournier S, Allison JP, Sharpe AH, Blazar BR. B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via R–T interactions. J Immunol. 2004;172:34–9.PubMed
31.
Zurück zum Zitat Mukherjee S, Ahmed A, Nandi D. CTLA4–CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with concanalin A. J Leuk Biol. 2005;78:144–57.CrossRef Mukherjee S, Ahmed A, Nandi D. CTLA4–CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with concanalin A. J Leuk Biol. 2005;78:144–57.CrossRef
32.
Zurück zum Zitat Bot A, Antohi S, Bot S, Garcia-Sastre A, Bona C. Induction of humoral and cellular immunity against influenza virus by immunization of newborn mice with a plasmid bearing a hemagglutinin gene. Int Immunol. 1997;9:1641–50.CrossRefPubMed Bot A, Antohi S, Bot S, Garcia-Sastre A, Bona C. Induction of humoral and cellular immunity against influenza virus by immunization of newborn mice with a plasmid bearing a hemagglutinin gene. Int Immunol. 1997;9:1641–50.CrossRefPubMed
33.
Zurück zum Zitat Weeratna RD, Brazolot Millan CL, McCluskie MJ, Davis HL. CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol. 2001;32:65–71.CrossRefPubMed Weeratna RD, Brazolot Millan CL, McCluskie MJ, Davis HL. CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol. 2001;32:65–71.CrossRefPubMed
34.
Zurück zum Zitat Rizzo MC, Arruda LK, Chapman MD, Fernandez-Caldas E, Baggio D, Platts-Mills TA, et al. IgG and IgE antibody responses to dust mite allergens among children with asthma in Brazil. Ann Allergy. 1993;71:152–8.PubMed Rizzo MC, Arruda LK, Chapman MD, Fernandez-Caldas E, Baggio D, Platts-Mills TA, et al. IgG and IgE antibody responses to dust mite allergens among children with asthma in Brazil. Ann Allergy. 1993;71:152–8.PubMed
35.
Zurück zum Zitat Sato MN, Oliveira CR, Futata EA, Victor JR, Maciel M, Fusaro AE, et al. Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin E. Clin Exp Allergy. 2002;32:1667–74.CrossRefPubMed Sato MN, Oliveira CR, Futata EA, Victor JR, Maciel M, Fusaro AE, et al. Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin E. Clin Exp Allergy. 2002;32:1667–74.CrossRefPubMed
36.
Zurück zum Zitat Carvalho AF, Fusaro AE, Oliveira CR, Brito CA, Duarte AJ, Sato MN. Blomia tropicalis and Dermatophagoides pteronyssinus mites evoke distinct patterns of airway cellular influx en type I hypersensitivity murine model. J Clin Immunol. 2004;24:533–41.CrossRefPubMed Carvalho AF, Fusaro AE, Oliveira CR, Brito CA, Duarte AJ, Sato MN. Blomia tropicalis and Dermatophagoides pteronyssinus mites evoke distinct patterns of airway cellular influx en type I hypersensitivity murine model. J Clin Immunol. 2004;24:533–41.CrossRefPubMed
37.
Zurück zum Zitat Kang H, Yu J, Yoo Y, Kim DK, Koh YY. Coincidence of atopy profile in terms of monosensitization and polysensitization in children and their parents. Allergy. 2005;60:1029–33.CrossRefPubMed Kang H, Yu J, Yoo Y, Kim DK, Koh YY. Coincidence of atopy profile in terms of monosensitization and polysensitization in children and their parents. Allergy. 2005;60:1029–33.CrossRefPubMed
38.
Zurück zum Zitat Sun CM, Deriaud E, Leclerc C, Lo-man R. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity. 2005;22:467–77.CrossRefPubMed Sun CM, Deriaud E, Leclerc C, Lo-man R. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity. 2005;22:467–77.CrossRefPubMed
39.
Zurück zum Zitat Walker WE, Goldstein DR. Neonatal B cells suppress innate toll-like receptor immune responses and modulate alloimmunity. J Immunol. 2007;179:1700–10.PubMed Walker WE, Goldstein DR. Neonatal B cells suppress innate toll-like receptor immune responses and modulate alloimmunity. J Immunol. 2007;179:1700–10.PubMed
40.
Zurück zum Zitat Durali D, De Goer De Herve MG, Giron-Michel J, Azzarone B, Delfraissy JF, Taoufik Y. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Blood. 2003;102:4084–9.CrossRefPubMed Durali D, De Goer De Herve MG, Giron-Michel J, Azzarone B, Delfraissy JF, Taoufik Y. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Blood. 2003;102:4084–9.CrossRefPubMed
41.
Zurück zum Zitat Harris DP, Goodrich S, Gerth AJ, Peng SL, FE SL. Regulation of IFN-γ production by B effector 1 cells: essential roles for T-bet and the IFN-γ receptor. J Immunol. 2005;174:6781–90.PubMed Harris DP, Goodrich S, Gerth AJ, Peng SL, FE SL. Regulation of IFN-γ production by B effector 1 cells: essential roles for T-bet and the IFN-γ receptor. J Immunol. 2005;174:6781–90.PubMed
42.
Zurück zum Zitat Gelman AE, Zhang J, Choi Y, Turka LA. Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol. 2004;172:6065–73.PubMed Gelman AE, Zhang J, Choi Y, Turka LA. Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol. 2004;172:6065–73.PubMed
43.
Zurück zum Zitat Coyle AJ, Gutierrez-Ramos JC. The role of ICOS and other costimulatory molecules in allergy and asthma. Springer Semin Immun. 2004;25:349–59.CrossRef Coyle AJ, Gutierrez-Ramos JC. The role of ICOS and other costimulatory molecules in allergy and asthma. Springer Semin Immun. 2004;25:349–59.CrossRef
Metadaten
Titel
CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice
verfasst von
Cyro A. de Brito
Ana E. Fusaro
Jefferson R. Victor
Paula O. Rigato
Adriana L. Goldoni
Bruno P. Muniz
Alberto J. S. Duarte
Maria N. Sato
Publikationsdatum
01.03.2010
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 2/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9358-9

Weitere Artikel der Ausgabe 2/2010

Journal of Clinical Immunology 2/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.