Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/27/2009
Publication Date: 5/22/2009
Publication URL: http:////www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005641
Citation: Olsen, I., Tollefsen, S., Aagaard, C., Reitan, L.J., Bannantine, J.P., Sollid, L.M., Lundin, K.E. 2009. Isolation of Mycobacterium avium Subspecies paratuberculosis Reactive CD4 T Cells from Intestinal Biopsies of Crohn's Disease Patients. PLoS One [serial online]. 4(5):e5641. Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005641. Interpretive Summary: This manuscript reports on the positive reaction of T cells (immune cells) isolated from intestinal tissue of Crohn’s disease patients when stimulated with different mycobacteria. These same T cells are not reactive with other kinds of bacteria tested. It is known that T cells are the principle arm of defense against intracellular pathogens such as Mycobacterium avium subsp paratuberculosis, the pathogen that causes Johne’s disease. The results of this study suggest that while mycobacteria may not cause Crohn’s disease, it may play some role in the pathogenesis of Crohn’s disease. This manuscript represents the first tangible efforts to develop collaborative research between ARS and the National Veterinary Institute in Norway. The seeds of this effort were sown with two independent visits by scientists to each country’s institutes and includes a memorandum of understanding signed by the director of the National Animal Disease Center and director of the National Veterinary Institute in Norway.
Technical Abstract: Crohn’s disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is still unknown. One hypothesis is that CD is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) in genetically predisposed individuals. MAP causes a similar disease in ruminants, and has been found in higher frequencies in CD patients. To address whether MAP contributes to the pathology we made T-cell lines from intestinal biopsies of patients with CD (n=11), ulcerative colitis (UC)(n=13) and control subjects (n=10). The T-cells from CD patients showed significantly higher proliferation in response to MAP compared to UC patients (p<0.05), while no differences in response to commensal bacteria were detected. T-cells clones (n= 28) were made from four CD patients and tested for response to various mycobacterial species. One T-cell clone responded only to MAP and the very closely related M. avium subspecies avium (MAA) while another responded to MAP, MAA and Mycobacterium intracellulare. The specificity of one clone was esxK. The T-cell clones produced IFN-gamma and/or IL-17 while minimal IL-4 was detected. The presence of MAP responsive T cells producing proinflammatory cytokines in CD patients, suggests that MAP or a very closely related mycobacterium may contribute to the pathogenesis of CD.