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Infection and Immunity, September 2002, p. 5148-5157, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5148-5157.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Ageing on the Immunoregulation of Parasitic Infection

Neil E. Humphreys,{dagger} and Richard K. Grencis*

School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

Received 29 January 2002/ Returned for modification 5 April 2002/ Accepted 2 May 2002

The plethora of changes associated with immunosenescence radically alters virtually all aspects of immune responsiveness. How this transformation effects resolution of an infectious challenge is addressed in this study. A well-established infection model was used; Trichuris muris, a cecum-dwelling helminth, is natural to mice, and infection in different strains results in clearly polarized responses. A dominating T helper 2 (Th2) response orchestrates immunity, whereas a Th1 response will result in susceptibility. Mice between 19 and 28 months old were more susceptible to infection, whereas 3-month-old mice of the same strain demonstrated the resistant phenotype. The cytokine response made by these aged mice was clearly altered at the site of infection, and within the local draining lymph nodes higher Th1 and lower Th2 cytokine levels were found, both at the protein and RNA level. Confirming these changes, aged mice also showed a delayed parasite-specific immunoglobulin G1 response and intestinal mastocytosis, both of which are driven by Th2 cytokines. To address possible causes of the observed immune deviation, purified CD4 cells from both young and aged mice were stimulated in vitro. Cells from aged mice did not respond to stimulation via CD28 and in vitro were less able to proliferate and polarize into Th2 cells; Th1 polarization was found to be normal. Together these data suggest that changes in cytokine phenotype, particularly CD4 cells, contribute to the observed age-associated switch from T. muris resistance to susceptibility.


* Corresponding author. Mailing address: School of Biological Sciences, 3.239, Stopford Building, The University of Manchester, Manchester M13 9PT, United Kingdom. Phone: 44 161 275 5238. Fax: 44 161 275 5640 E-mail: Richard.K.Grencis{at}man.ac.uk.

Editor: R. N. Moore

{dagger} Present address: H1.8, Syngenta CTL, Alderley Park, Macclesfield, Cheshire SK10 4TJ, United Kingdom.


Infection and Immunity, September 2002, p. 5148-5157, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5148-5157.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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