Development of the appropriate CD4^+ T helper (T_H) subset during an immune response is important for disease resolution. With the use of naive, ovalbumin-specific αβ T cell receptor transgenic T cells, it was found that heat-killed Listeria monocytogenes induced T_H1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress T_H1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate T_H1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate T_H phenotype.