title: Progressive bovine paratuberculosis is associated with local loss of CD4(+) T cells, increased frequency of gamma delta T cells, and related changes in T-cell function.
abstract: Bovine paratuberculosis is caused by the infection of young calves with Mycobacterium avium subsp. paratuberculosis, resulting in a chronic granulomatous infection of predominantly the ileum. After an incubation period of 2 to 5 years, the disease becomes progressive in some of the chronically infected, but asymptomatic cows. This results in a protein-losing enteropathy that will ultimately be fatal. A loss of cell-mediated immune responses in symptomatic animals has been described, but no information is available concerning immune reactivity in the intestine. We sought to investigate putative disease status-associated lymphocyte subset distributions and antigen-specific functional characteristics of mononuclear cells isolated from blood, gut-associated lymphoid tissue, and the intestinal walls of 22 cows in different stages of disease and in control animals. The results demonstrated a significant decrease in CD4(+) T-cell frequency and a significant increase in TcR1-N12(+) gamma delta T-cell frequency in ileum lamina propria lymphocytes of symptomatic animals compared to the asymptomatic shedders. Immunohistology revealed that there was also an absolute decrease in the number of CD4(+) T cells in sections of the lesional ileum. Our findings also indicated that both peripheral and intestinal cell-mediated responses are decreased in symptomatic animals compared to asymptomatic animals. We conclude that the decrease in cell-mediated responses is likely related to a loss of antigen-specific CD4(+) T cells, which is most prominent in the lesional ileum from symptomatic animals, thus contributing to the progressive nature of bovine paratuberculosis.
authors.affiliation: Immunology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands. a.p.koets@vet.uu.nl
authors.forename: Ad
authors.initials: A
authors.lastname: Koets
authors.forename: Victor
authors.initials: V
authors.lastname: Rutten
authors.forename: Aad
authors.initials: A
authors.lastname: Hoek
authors.forename: Frans
authors.initials: F
authors.lastname: van Mil
authors.forename: Kerstin
authors.initials: K
authors.lastname: Müller
authors.forename: Douwe
authors.initials: D
authors.lastname: Bakker
authors.forename: Erik
authors.initials: E
authors.lastname: Gruys
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D002455:Cell Division; D018834:Chaperonin 60 / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D007080:Ileocecal Valve / Q000382:microbiology; D007082:Ileum / Q000276:immunology / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology; D010283:Paratuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014373:Tuberculin / Q000494:pharmacology
chemical_list: D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014373:Tuberculin; D003208:Concanavalin A