title: Regulatory T cells in cattle and their potential role in bovine paratuberculosis.
abstract: The intracellular bacterium Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease in wild and domestic ruminants. Johne's disease presents as a chronic enteritis with severe inflammation of intestinal tissues, characterized by widespread infiltration of macrophages, the target cell of MAP. Clinical signs of Johne's disease are typically accompanied by a loss of peripheral CD4+ T cell responses to MAP antigens and an increase in anti-MAP serum IgG levels. Recently, it was proposed that regulatory T cells might develop over the lengthy course of subclinical MAP infection. In the past five years, significant progress in defining bovine regulatory T cells has been made. These studies grew out of observations that IL-10 is produced by PBMCs in response to MAP antigen stimulation and that neutralization of this IL-10 could enhance IFN-γ production from MAP-antigen reactive effector T cells. Depletion studies revealed that MAP responsive cell populations producing IL-10 were largely CD4+ and CD25+, although monocytes have also been shown to produce IL-10 in response to MAP. In addition, evidence for a regulatory population of γδ T cells has also begun to accumulate. We summarize current thinking regarding regulatory T cells in MAP infection and provide data suggesting a potential link between regulatory T cells, bovine leukemia virus, and MAP.
authors.affiliation: Molecular Pathogenesis Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA. coussens@msu.edu
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coussens
authors.forename: Sue
authors.initials: S
authors.lastname: Sipkovsky
authors.forename: Brooke
authors.initials: B
authors.lastname: Murphy
authors.forename: Jon
authors.initials: J
authors.lastname: Roussey
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Colvin
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002417:Cattle / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D002418:Cattle Diseases / Q000276:immunology* / Q000382:microbiology; D060085:Coinfection; D016583:Enzootic Bovine Leukosis / Q000473:pathology / Q000821:virology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D001909:Leukemia Virus, Bovine / Q000276:immunology / Q000472:pathogenicity; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology / Q000472:pathogenicity; D010283:Paratuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D016753:Interleukin-10; D007371:Interferon-gamma