Effect of inducible costimulator blockade on the pathological and protective immune responses induced by the gastrointestinal helminth Trichinella spiralis

Scales, H. E. , Ierna, M. X., Gutierrez-Ramos, J.-C., Coyle, A. J., Garside, P. and Lawrence, C. E. (2004) Effect of inducible costimulator blockade on the pathological and protective immune responses induced by the gastrointestinal helminth Trichinella spiralis. European Journal of Immunology, 34, pp. 2854-2862. (doi: 10.1002/eji.200324364) (PMID:5368302)

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Abstract

Infections with gastrointestinal helminths elicit potent Th2 responses, which ultimately result in their expulsion. However, during expulsion of Trichinella spiralis this Th2 response also induces a severe enteropathy characterized by villus atrophy and crypt hyperplasia. Inducible costimulator (ICOS), a homologue of CD28, interacts with B7-related protein 1, and has been shown to be important in T-B cell interactions and antibody class switching. Significantly, ICOS appears to be involved in the induction of both Th1 and Th2 responses, but may be of heightened importance in Th2 responses. Here we employed a blocking antibody against ICOS to investigate the contribution of ICOS costimulation to the development of the protective and pathological immune responses induced during infection with T. spiralis. We show that, although blocking ICOS resulted in a decrease in TNF-α and the Th2 cytokines IL-4 and IL-5 and serum levels of total IgE, it did not affect the expulsion of the adult parasites. Surprisingly, levels of IL-9, IL-13 and IL-10 were elevated and protection against the larval muscle stage of the parasite was enhanced. Importantly, these findings may relate to the fact that ICOS blockade significantly ameliorated the enteropathy that usually accompanies expulsion of the adult parasite.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and Scales, Dr Hannah
Authors: Scales, H. E., Ierna, M. X., Gutierrez-Ramos, J.-C., Coyle, A. J., Garside, P., and Lawrence, C. E.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-414
Published Online:05 August 2004

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