Analysis of antigen-specific proliferation and IL-2/IL-4 production of spleen cells from mice infected with mycobacterium bovis bcg

The present study was performed in order to define the responding populations and profiles of cytokine production in BCG-primed spleen cells restimulated in vitro with antigen. Spleen cells from DBA/2 mice, one of BCG-resistant strains (Bcg^r), infected with Mycobacterium bovis BCG vigorously proliferated by restimulation with heat-killed BCG. This response peaked as early as on day 3 after BCG infection, and then decreased to the basal level by 3 weeks. Blocking of IL-2Rα chain or IL-4 by each antibody partially inhibited it, but anti-IFN-γ antibody did not, suggesting that both IL-2 and IL-4 were involved in the proliferation of primed spleen cells. CD4+and γδ TCR-bearing T cell were responding populations to BCG, but CD8⁺T cell was not, because depletion of CD4+ or γδ T cells by the treatment with each antibody and complement inhibited proliferation and IL-2/IL-4 production, but that of CD8⁺ T cells did not. Further study demonstrated that spleen cells from BCG-resistant DBA/2 mice produced more IL-2/IL-4 than those from BALB/c mice, one of BCG-susceptible strains (Bcg^s), in response to BCG. These results suggest that both CD4⁺ and γδTCR-bearing T cells play an important role in the host defense against M. bovis BCG infection, and that the magnitude of cytokine production is one of the critical factors to define the susceptibility of mice to this pathogen in the late phase of infection.