Temporal Mycobacterium paratuberculosis infection in T-cell receptor (TCR)-α and TCR-δ-deficient mice

Mycobacterium paratuberculosis is the causative agent of paratuberculosis (Johne’s disease), a chronic inflammation of the terminal portion of the ileum in ruminants. The predominance of cell-mediated immunity in early stages of the disease suggests that T lymphocytes are essential to protect the host from infection with M. paratuberculosis. In this study, we investigated the role of αβ and γδ T cells in resistance to M. paratuberculosis infection using a T-cell receptor (TCR) knockout mouse model. Weanling TCR-α-deficient, TCR-δ-deficient, and C57BL/6 control mice (5–6 weeks of age) were acclimated for 2 weeks and then inoculated intraperitoneally with 108 CFU/ml of M. paratuberculosis (either strain 19698 or strain Ben). Groups of mice within each treatment group were euthanized at 1, 3 and 6 months post-inoculation. Sections of spleen, liver, ileum and mesenteric lymph node were prepared for bacterial culture and histologic examination. At all time points of infection and regardless of bacterial strain, TCR-α-deficient mice had higher levels of M. paratuberculosis colonization in their tissues compared to TCR-δ-deficient mice or C57BL/6 control mice. Lesions were located predominately in the liver and the ileum, depending upon period of infection, and lesion scores were higher for TCR-α-deficient mice compared to the other treatment groups. These results suggest that αβ T cells play a major role in resistance to infection with M. paratuberculosis and that γδ T cells may play a lesser role and potentially confound protective immune responses.