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Infection and Immunity, July 2002, p. 3856-3864, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3856-3864.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Ad Koets,1* Victor Rutten,1 Aad Hoek,1 Frans van Mil,2 Kerstin Müller,3 Douwe Bakker,4 Erik Gruys,2 and Willem van Eden1

Immunology Division, Department of Infectious Diseases and Immunology,1 Department of Pathology,2 Department of Farm Animal Health Faculty of Veterinary Medicine, Utrecht University, Utrecht,3 Department of Bacteriology, Institute for Animal Science and Health, Lelystad, The Netherlands4

Received 2 October 2001/ Returned for modification 14 December 2001/ Accepted 11 March 2002

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.

* Corresponding author. Mailing address: Immunology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.165, 3508 TD Utrecht, The Netherlands. Phone: 31-30-2534608. Fax: 31-30-2533555. E-mail: a.p.koets{at}vet.uu.nl.

Editor: S. H. E. Kaufmann

Infection and Immunity, July 2002, p. 3856-3864, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3856-3864.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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