Pathogen-induced Th1 phenotype development in CD4+ alpha beta-TCR transgenic T cells is macrophage dependent.
We used an ovalbumin (OVA)-specific alpha beta-TCR transgenic mouse system to examine the cellular basis of CD4+ T helper (Th) phenotype development in vitro. Heat-killed Listeria monocytogenes (HKLM) strongly promotes the in vitro development of a Th1 phenotype in OVA-specific transgenic T cells. Listeria monocytogenes effects to promote the Th1 phenotype are antigen presenting cell (APC) dependent and occur when splenic 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 Th1 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 gamma is necessary for Listeria induction of Th1 development, IFN-gamma alone is insufficient to induce Th1 development. Furthermore, Listeria induction of the Th1 phenotype does not require several known products of activated macrophages, including interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha), IL-6, or nitric oxide. Although transforming growth factor-beta (TGF-beta) may mediate some Listeria effects, it does not fully reconstitute Listeria effects to promote Th1 development. In summary, host interactions with bacterial pathogens can affect the development of specific Th subsets, allowing innate immune cells to direct development of specific immune phenotype. For Listeria monocytogenes, the induction of the Th1 phenotype may involve a novel cytokine distinct from several known factors produced by activated macrophages.
Department of Pathology, Washington University School of Medicine, St Louis, MO 63110.
C S
CS
Hsieh
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SE
Macatonia
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A
O'Garra
K M
KM
Murphy
D000818:Animals; D015704:CD4 Antigens; D016207:Cytokines / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D015704:CD4 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin