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Publication : Genetic dissection of primary and secondary responses to a widespread natural pathogen of the gut, Eimeria vermiformis.

First Author  Smith AL Year  2000
Journal  Infect Immun Volume  68
Issue  11 Pages  6273-80
PubMed ID  11035735 Mgi Jnum  J:133107
Mgi Id  MGI:3777733 Doi  10.1128/iai.68.11.6273-6280.2000
Citation  Smith AL, et al. (2000) Genetic dissection of primary and secondary responses to a widespread natural pathogen of the gut, Eimeria vermiformis. Infect Immun 68(11):6273-80
abstractText  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.
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