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Infection and Immunity, November 2000, p. 6273-6280, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Genetic Dissection of Primary and Secondary Responses to a Widespread Natural Pathogen of the Gut, Eimeria vermiformis

Adrian L. Smith1,2 and Adrian C. Hayday1,3,*

Department of Molecular Cell and Developmental Biology, Yale University, New Haven, Connecticut,1 and Institute for Animal Health, Compton, Berkshire,2 and Department of Immunobiology, GKT School of Medicine, University of London, London,3 United Kingdom

Received 12 June 2000/Returned for modification 22 July 2000/Accepted 3 August 2000

Because most pathogens initially challenge the body at epithelial surfaces, it is important to dissect the mechanisms that underlie T-cell responses to infected epithelial cells in vivo. The coccidian parasites of the genus Eimeria are protozoan gut pathogens that elicit a potent, protective immune response in a wide range of host species. CD4+ alpha beta T cells and gamma interferon (IFN-gamma ) are centrally implicated in the primary immunoprotective response. To define any additional requirements for the primary response and to develop a comparison between the primary and the secondary response, we have studied Eimeria infections of a broad range of genetically altered mice. We find that a full-strength primary response depends on beta 2-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-gamma and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase. Indeed, MHC class II-deficient and IFN-gamma -deficient mice are as susceptible to primary infection as mice deficient in all alpha beta T cells. Strikingly, the requirements for a highly effective alpha beta -T-cell-driven memory response are less stringent, requiring neither IFN-gamma nor IL-6 nor class I MHC. The class II MHC dependence was also reduced, with adoptively transferable immunity developing in MHC class II-/- mice. Besides the improved depiction of an immune response to a natural gut pathogen, the finding that effective memory can be elicited in the absence of primary effector responses appears to create latitude in the design of vaccine strategies.


* Corresponding author. Mailing address: The Peter Gorer Department of Immunobiology, Guy's, King's and St Thomas' Medical School, King's College London, 3rd Floor New Guy's House, Guy's Hospital, London, SE1 9RT, United Kingdom. Phone: 44 020 7955 4355. Fax: 44020 7955 4961. E-mail: adrian.hayday{at}kcl.ac.uk.


Infection and Immunity, November 2000, p. 6273-6280, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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