Bacille Calmette Guérin and interleukin-12 down-modulate interleukin-4-producing CD4+ NK1+ T lymphocytes

Early production of interleukin-12 (IL-12) by macrophages and of IL-4 from CD4+ NK1+ T cells influence development of the acquired immune response against infectious agents, namely differentiation of interferon-gamma-secreting T helper 1 (Th1) cells against intracellular pathogens and of IL-4-producing Th2 cells against helminths. Evidence has been presented for transient convertibility of Th1 and Th2 cells in the presence of the polarizing cytokines IL-4 or IL-12, respectively. Moreover, it is likely that IL-4 dominates over IL-12, suggesting that Th2 cell development is preferred in the presence of both cytokines. Mycobacterium bovis Bacille Calmette Guerin (BCG) and IL-12 are potent inducers of Th1 responses. Here we show that BCG and IL-12 down-modulate IL-4-producing CD4+ NK1+ TCR alpha/beta(intermediate) liver lymphocytes. Our data provide further insights into the mechanisms by which BCG and IL-12 may promote unrestricted development of Th1 responses in vivo: BCG and IL-12 not only provide the positive stimuli for Th1 cell differentiation, but also interfere with antagonizing signals.