Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2004
Publication Date: 11/14/2004
Citation: Koo, H.C., Park, Y.H., Hamilton, M.J., Barrington, G.M., Davies, C.J., Kim, J.B., Dahl, J.L., Waters, W.R., Davis, W.C. 2004. Analysis of the immune response to Mycobacterium avium subsp. paratuberculosis in experimentally infected calves. Infection and Immunity. 72:6870-6883. Interpretive Summary: Johne’s disease of cattle is ubiquitous causing serious economic losses to the dairy industry due to decreased health and production of affected animals. A major impediment in the study of this disease is the lack of a reproducible experimental model of infection in the target host (i.e., cattle). In the present study we describe a method to infect very young cattle with the bacterium that causes this serious disease. In addition, we describe the immune response induced by infection in these animals. Findings from the present study will be useful for the development of improved methods to diagnose and prevent this chronic disease of cattle.
Technical Abstract: Johne's disease of cattle is widespread and causes significant economic loss to producers. Control has been hindered by limited understanding of the immune response to the causative agent, M. avium subsp. paratuberculosis (Map) and lack of an effective vaccine and sensitive specific diagnostic assays. The present study was conducted to gain insight into factors affecting the immune response to Map. A persistent proliferative response to Map purified protein derivative and soluble Map antigens was detected in orally infected neonatal calves 6 months post infection (PI) by flow cytometry (FC). CD4+ T cells with a memory phenotype (CD45R0+) expressing CD25 and CD26 were the predominant cell type responding to antigens. Few CD8+ T cells proliferated in response to antigens until 18 months PI. Gamma delta T cells did not appear to respond to antigen until 18 months PI. The majority of WC1+ CD2- and a few WC1- CD2+ gamma delta T cells expressed CD25 at T0. By 18 months, however, subsets of gamma delta T cells from both control and infected animals showed an increase in expression of CD25, ACT2, and CD26 in the presence of the antigens. Two populations of CD3- non T non B null cells, CD2+ and CD2-, proliferated in cell cultures from some control and infected animals during the study, with and without antigen. The studies clearly show multicolor FC offers a consistent reliable way to monitor the evolution and changes in the immune response to Map that occur during disease progression.