Mycobacterium bovis BCG-induced Th1 type CD4+ suppressor T cells act by suppressing IL-2 production and IL-2 receptor expression.

Induction of suppressor cells has been hypothesized to explain the variability in the efficacy of Mycobacterium bovis BCG vaccination against mycobacterial diseases. In this study, we induced suppressor T cells by in vitro stimulation of peripheral blood mononuclear cells obtained from BCG-vaccinated healthy subjects. These suppressor T cells were CD4+ and did not affect interleukin-1 production by adherent cells in response to BCG. However, they suppressed interleukin-2 (IL-2) production and IL-2 receptor expression by the responding cells. Exogenous addition of IL-2 could partially restore the responsiveness of the indicator cells. To further characterize the cells responsible for suppression, T cell clones were established by limiting dilution. All the established T cell clones expressed CD4 marker, proliferated in response to BCG, were cytotoxic for antigen-presenting cells, and suppressed the antigen-induced proliferation of the indicator cells. Both suppression and cytotoxicity were not mediated by soluble factors but required cell-to-cell contact and were HLA-class II restricted. These results suggest that preferential killing of antigen-presenting cells by CD4+ T cells may be responsible for in vitro observed suppression in our system.