Pathogen-induced Th1 phenotype development in CD4⁺ αβ-TCR transgenic T cells is macrophage dependent

We used an ovalbumin (OVA)-specific αβ-TCR transgenic mouse system to examine the cellular basis of CD4⁺T helper (T_h) phenotype development in vitro. Heat-killed Listerla monocytogenes (HKLM) strongly promotes the in vitro development of a T_h1 phenotype in OVA-specific transgenic T cells. Listeria monocytogenes effects to promote the T_h1 phenotype are antigen presenting cell (APC) dependent and occur when spienic APCs, but not the B cell hybridoma TA3, are present during T cell activation. However, addition of FACS-sorted macrophages to TA3 activated cultures restores the ability of Listeria to induce T_h1 development. This effect on T cell development does not require MHC-restricted antigen presentation by macrophages, but may act through soluble factors. Although the presence of interferon γ is necessary for Listeria induction of T_h1 development, IFN-γ alone is insufficient to induce T_h1 development. Furthermore, Listeria induction of the T_h1 phenotype does not require several known products of activated macrophages, including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), IL-6, or nitric oxide. Although transforming growth factor-β (TGF-β) may mediate some Listeria effects, it does not fully reconstitute Listerla effects to promote T_h1 development. In summary, host interactions with bacterial pathogens can affect the development of specific T_h subsets, allowing Innate Immune cells to direct development of specific Immune phenotype. For Listeria monocytogenes, the induction of the T_h1 phenotype may involve a novel cytokine distinct from several known factors produced by activated macrophages.