THE IN-VIVO EFFECTS OF NEUTRALIZING ANTIBODIES AGAINST IFN-GAMMA, IL-4, OR IL-10 ON THE HUMORAL IMMUNE-RESPONSE IN YOUNG AND AGED MICE

In the present study we investigated whether age-related changes in th e composition and functional properties of murine CD4(+) T cells are r eflected in vivo by a changed humoral response to influenza vaccine in aged mice. After the primary immunization, the titers of influenza-sp ecific IgM, IgG1, IgG2a, and IgG2b, but not of IgG3 and IgE, were sign ificantly reduced in aged mice compared to young mice. Treatment of ag ed mice with anti-IFN-gamma, anti-IL-4, or anti-IL-10 resulted in leve ls of IgM and IgG1 comparable to those found in young mice, whereas Ig G2a and IgG2b were further decreased. After the booster immunization I gE was significantly enhanced in aged mice, whereas no differences wer e observed with regard to the other isotypes. During the primary respo nse in young mice, anti-IFN-gamma 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 decr eased IgG2b and IgG3. During the primary response in aged mice, all an ti-cytokine antibodies enhanced IgM and IgG1 while IgE was only enhanc ed by anti-IL-10. By contrast, IgG3 was inhibited by anti-IFN-gamma an d anti-IL-10. Anti-cytokine treatment of young mice increased all isot ypes, except IgG3, in the secondary response, whereas the secondary re sponse in aged mice was largely insensitive to anti-cytokine treatment . These data therefore support the idea that the in vivo effects of cy tokines on isotype switching are dependent on the differentiation stag e of B cells which may be different in young and aged mice. (C) 1995 A cademic Press,Inc.