Experimental infection of mice with the intracellular bacterium, Listeria monocytogenes, provides a paragon model for immune defence dominated by T helper type 1 (Th1) responses. Potent production of interleukin (IL)-12 by infected macrophages is considered the determining factor in Th1 cell development. In contrast, it is assumed that IL-4 producers remain virtually unstimulated in listeriosis. In the liver, the major target organ of listeriosis, an unusual T lymphocyte population exists with the intriguing phenotype CD4+NK1.1+ TCRα/βintermediate (TCRα/βint). Here we show that IL-4-producing CD4+NK1.1+TCRα/βint liver lymphocytes are down-regulated early in listeriosis. We assume that curtailment of IL-4-producing CD4+NK1.1+TCRα/βint liver lymphocytes promotes unconstrained development of Th1 cells which are central to protection against intracellular bacteria.