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Infection and Immunity, November 2000, p. 6273-6280, Vol. 68, No. 11
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+
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

T cells and gamma interferon (IFN-
) 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
2-microglobulin (class I major
histocompatibility complex [MHC] and class II MHC and on IFN-
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-
-deficient mice are as susceptible to primary infection as mice
deficient in all 
T cells. Strikingly, the requirements for a
highly effective 
-T-cell-driven memory response are less
stringent, requiring neither IFN-
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.
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