Defective in vivo induction of functional type 2 cytokine responses in aged mice

Eur J Immunol. 2001 May;31(5):1495-502. doi: 10.1002/1521-4141(200105)31:5<1495::AID-IMMU1495>3.0.CO;2-8.

Abstract

Aged mice have various defects in their immune system. We report that following in vivo challenge with type 2 cytokine-inducing Schistosoma mansoni eggs, aged mice fail to produce type 2 cytokines and also have impaired antigen-specific antibody production. Using two separate type 2 cytokine-dependent in vivo models, the synchronous pulmonary schistosome egg granuloma model and infection with the gastro-intestinal nematode Nippostrongylus brasiliensis, aged mice were shown to have a dramatically impaired capacity to elicit a functional type 2 response, i. e. respectively, impaired pulmonary granulomas and delayed rejection of intestinal worms. Aged mice did not develop eosinophilia and had impaired production of antigen specific IgE. Defective induction of type 2 responses was associated with negligible IL-2 and elevated IFN-gamma production by cells from aged mice. Naive aged mice had increased numbers of Th1, Th2 and Tc1 cells compared to young animals. In vivo type 2 challenge increased the frequencies of Th1 and Tc1 cells and reducing Th2 cell numbers in aged mice. These data demonstrate that a consequence of ageing is a profound in vivo defect in the capacity to elicit type 2 cytokine responses and such an impairment in type 2 responsiveness may account for the increased incidence of various type 1 cytokine-mediated diseases in aged individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Cells, Cultured
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophilia / immunology
  • Female
  • Immunization
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nippostrongylus / immunology
  • Ovum / immunology
  • Plasma Cell Granuloma, Pulmonary / immunology
  • Schistosoma / immunology
  • Strongylida Infections / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Time Factors

Substances

  • Cytokines
  • Interleukin-4
  • Interferon-gamma