Genetic dissection of primary and secondary responses to a widespread natural pathogen of the gut, Eimeria vermiformis.
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.
Smith
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Department of Molecular Cell and Developmental Biology, Yale University, New Haven, Connecticut, USA.
Hayday
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D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000502:physiology; D004539:Eimeria / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D018949:Antigens, CD1; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma