Vaccination of goat kids against paratuberculosis protects against lesions and clinical disease. The systemic cellular response was studied in goat kids 3-9 weeks after vaccination. Peripheral blood cells showed increased interferon-gamma production and expression of interleukin-2 receptor (CD25) after stimulation with Mycobacterium avium subsp. paratuberculosis antigens. The lymph node draining the vaccination granuloma was studied three weeks after vaccination in a parallel group of goat kids. In deep cortex, MHCII+ cells were observed surrounded by CD4+ T-cells, while follicular hypertrophy and hyperplasia were prominent in the subcapsular region and along connective tissue trabecula. Comparison of the local and systemic immune responses revealed an inverse relationship between CD25+ T-cells in the lymph node deep cortex and cells in peripheral blood that up-regulate CD25 upon in vitro stimulation, suggesting that activated and regulatory T-cells in the local lymph node influence the level of circulating antigen-specific T-cells following vaccination against paratuberculosis in goats.