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The in vivo effects of neutralizing antibodies against IFN-γ, IL-4, or IL-10 on the humoral immune response in young and aged mice

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Author: Dobber, R. · Tielemans, M. · Nagelkerken, L.
Type:article
Date:1995
Institution: TNO Preventie en Gezondheid
Source:Cellular Immunology, 2, 160, 185-192
Identifier: 232951
doi: DOI:10.1016/0008-8749(95)80026-F
Keywords: Biology · gamma interferon · gamma interferon antibody · immunoglobulin g1 · immunoglobulin g2a · immunoglobulin g2b · immunoglobulin g3 · immunoglobulin m · influenza vaccine · interleukin 10 · interleukin 10 antibody · interleukin 4 · interleukin 4 antibody · monoclonal antibody · unclassified drug · aged · animal experiment · article · b lymphocyte · controlled study · humoral immunity · immunization · influenza · intraperitoneal drug administration · mouse · nonhuman · priority journal · t lymphocyte · Aging · Animal · Antibodies, Monoclonal · Antibodies, Viral · Antibody Formation · CD4-Positive T-Lymphocytes · Comparative Study · Female · Hemagglutinin Glycoproteins, Influenza Virus · Hemagglutinins, Viral · Immunization, Secondary · Immunoglobulin Class Switching · Immunoglobulin E · Immunoglobulin G · Immunoglobulin M · Influenza A Virus, Human · Influenza Vaccine · Interferon Type II · Interleukin-10 · Interleukin-4 · Mice · Mice, Inbred CBA · Neuraminidase · Vaccination · Animalia · Murinae

Abstract

In the present study we investigated whether age-related changes in the composition and functional properties of murine CD4+ T cells are reflected in vivo by a changed humoral response to influenza vaccine in aged mice. After the primary immunization, the titers of influenza-specific IgM, IgG1, IgG2a, and IgG2b, but not of IgG3 and IgE, were significantly reduced in aged mice compared to young mice. Treatment of aged mice with anti-IFN-γ, anti-IL-4, or anti-IL-10 resulted in levels of IgM and IgG1 comparable to those found in young mice, whereas IgG2a and IgG2b were further decreased. After the booster immunization IgE was significantly enhanced in aged mice, whereas no differences were observed with regard to the other isotypes. During the primary response in young mice, anti-IFN-γ stimulated IgG1 and IgE, whereas an inhibition of IgG2a, IgG2b, and IgG3 was observed. Anti-IL-4 caused a decrease only in IgG3 while anti-IL-10 increased IgM and IgG1 and decreased IgG2b and IgG3. During the primary response in aged mice, all anti-cytokine antibodies enhanced IgM and IgG1 while IgE was only enhanced by anti-IL-10. By contrast, IgG3 was inhibited by anti-IFN-γ and anti-IL-10. Anti-cytokine treatment of young mice increased all isotypes, except IgG3, in the secondary response, whereas the secondary response in aged mice was largely insensitive to anti-cytokine treatment. These data therefore support the idea that the in vivo effects of cytokines on isotype switching are dependent on the differentiation stage of B cells which may be different in young and aged mice. Chemicals/CAS: Antibodies, Monoclonal; Antibodies, Viral; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Immunoglobulin E, 37341-29-0; Immunoglobulin G; Immunoglobulin M; Influenza Vaccine; Interferon Type II, 82115-62-6; Interleukin-10, 130068-27-8; Interleukin-4, 207137-56-2; Neuraminidase, EC 3.2.1.18