Dendritic cells (DC) are of central importance in the initiation of T cell-mediated adaptive immunity because these professional phagocytes internalize, process, and present microbial antigens to T lymphocytes. T lymphocytes have a pivotal role in controlling and clearing infection with intracellular pathogens through cytokine production. T lymphocytes also can mediate direct lysis of infected cells or activate B and T cells. In this article, we report that DC, when cocultured with Salmonella, fail to efficiently stimulate T cells for proliferation. We show that the failure of T lymphocytes to respond to Salmonella-infected DC is not simply due to Salmonella-induced programmed DC death or interference with up-regulation of costimulatory molecules CD80 and CD86. We cocultured bacteria with purified T lymphocytes, and we demonstrate here that Salmonella have a direct, contact-dependent inhibitory effect on the T cells, even in the absence of DC. This direct, Salmonella-induced inhibitory effect reduces the ability of T cells to proliferate and produce cytokines in response to stimulation and appears to require live bacteria. Cumulatively, these results are evidence that Salmonella may interfere with the development of acquired immunity, providing insights into the complex nature of this hostpathogen interaction.