Progressive Bovine Paratuberculosis Is Associated with Local Loss of CD4 + T Cells, Increased Frequency of γδ T Cells, and Related Changes in T-Cell Function

Author:

Koets Ad1,Rutten Victor1,Hoek Aad1,van Mil Frans2,Müller Kerstin3,Bakker Douwe4,Gruys Erik2,van Eden Willem1

Affiliation:

1. Immunology Division, Department of Infectious Diseases and Immunology

2. Department of Pathology

3. Department of Farm Animal Health Faculty of Veterinary Medicine, Utrecht University, Utrecht

4. Department of Bacteriology, Institute for Animal Science and Health, Lelystad, The Netherlands

Abstract

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 + γδ 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

Reference47 articles.

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2. Alzuherri, H. M., C. J. Woodall, and C. J. Clarke. 1996. Increased intestinal TNF-α, IL-1β and IL-6 expression in ovine paratuberculosis. Vet. Immunol. Immunopathol.49:331-345.

3. Baldwin, C. L., A. J. Teale, J. G. Naessens, B. M. Goddeeris, N. D. MacHugh, and W. I. Morrison. 1986. Characterization of a subset of bovine T lymphocytes that express BoT4 by monoclonal antibodies and function: similarity to lymphocytes defined by human T4 and murine L3T4. J. Immunol.136:4385-4391.

4. Bendixen, P. H. 1978. Immunological reactions caused by infection with Mycobacterium paratuberculosis: a review. Nord. Vet. Med.30:163-168.

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