Defective in vivo induction of functional type 2 cytokine responses in aged mice.
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.
Smith
P
P
Department of Pathology, University of Cambridge, GB.
Dunne
D W
DW
Fallon
P G
PG
D000375:Aging / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology; D010063:Ovum / Q000276:immunology; D016726:Plasma Cell Granuloma, Pulmonary / Q000276:immunology; D012547:Schistosoma / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma