IMMUNOLOGY AND INTERVENTION STRATEGIES FOR JOHNE'S DISEASE
Location: Infectious Bacterial Diseases Research Unit
Title: Depletion of CD4 T Lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 23, 2012
Publication Date: October 15, 2012
Citation: Allen, A.J., Stabel, J.R., Robbe-Austerman, S., Park, K.T., Palmer, M.V., Barrington, G.M., Lahmers, K.K., Hamilton, M.J., Davis, W.C. 2012. Depletion of CD4 T lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression. Veterinary Immunology and Immunopathology. 149(3-4):286-291.
Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle,sheep and wild ruminants, characterized by diarrhea, reduced feed intake, weight loss and death. Animals usually become infected when they are young by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced production by these animals through reduced milk production, they also present a potential infective threat to the rest of the herd. Johne’s disease is difficult to diagnose and therefore to control. Animal infection models are necessary for the study of host responses to infection under controlled conditions. In this paper, calves were depleted of T cells prior to infection to determine if that would cause more disease. An ileal cannula was placed in calves to allow direct placement of the bacteria into the target tissue. Results of this study suggest that depleting calves of T cells prior to infection did not cause an increased number of bacteria in the tissues. This type of study will aid in the evaluation of new vaccines to prevent infection and disease.
A calf model was used to determine if the depletion of CD4 T cells prior to inoculation of Mycobacterium avium subsp. paratuberculosis (Map) would delay development of an immune response to Map and accelerate disease progression. Ileal cannulas were surgically implanted in 5 bull calves at two months of age. Two calves were depleted of CD4 T cells by intravenous injection of anti-bovine CD4 antibody administered 24 hours prior to inoculation with Map. The two CD4-depleted calves and one non-depleted calf were inoculated via ileal cannula with 1x10**8 cfu live Map. Two additional calves served as non-depleted and uninfected controls. Injection with the anti-CD4 mAb reduced the frequency of CD4 T cells from a pre-depletion average of 15% to less than 1% in PBMC at 24 hours. However, a consistent proliferative response, dominated by CD4 T cells, developed in both treated and untreated calves over the course of the 6-month study period. Recovery of Map from serial biopsies obtained from the CD4-depleted and non-depleted calves after Map infection did not differ. In addition, CD4 depletion did not increase the level of Map shed in the feces, with more consistent shedding observed for the non-depleted calf during the infection period.