Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-κB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.
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We thank C. A. Janeway and R. A. Flavell for the 1H3.1 TCR–transgenic and caspase-1–deficient mice, respectively. R. M. thanks C. A. Janeway for critical reading of the manuscript and continuous support. Supported by Howard Hughes Medical Institute, NIH (AI44220-01) and Searle (to R. M.) and by Deutsche Forschungsgemeinschaft (to M. S.).
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