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

• Published in: Journal of clinical immunology Vol. 30; no. 2; pp. 280 - 291
• Main Authors: de Brito, Cyro A, Fusaro, Ana E, Victor, Jefferson R, Rigato, Paula O, Goldoni, Adriana L, Muniz, Bruno P, Duarte, Alberto J. S, Sato, Maria N
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.03.2010; Springer US; Springer Nature B.V
• Subjects: Animals; Animals, Newborn; Antigens, Dermatophagoides - administration & dosage; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; B7-1 Antigen - biosynthesis; B7-1 Antigen - genetics; Biomedical and Life Sciences; Biomedicine; Cell Extracts - administration & dosage; DNA - administration & dosage; Female; Hypersensitivity - blood; Hypersensitivity - immunology; Immunity, Humoral; Immunization; Immunoglobulin E - blood; Immunology; Infectious Diseases; Internal Medicine; Medical Microbiology; Mice; Mice, Inbred Strains; Oligodeoxyribonucleotides; Ovalbumin - administration & dosage; Pyroglyphidae; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Toll-Like Receptor 9 - biosynthesis; Toll-Like Receptor 9 - genetics; Oligodeoxynucleotide; immunomodulation; neonate; CpG; costimulatory molecules
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-009-9358-9

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.