Generation of Salmonella-specific Th1 cells requires sustained antigen stimulation

The administration of live attenuated Salmonella strains has proven to be an effective way to generate protective immunity against Salmonella infection in humans and mice. Studies in the mouse model have shown that protection requires Salmonella-specific Th1 cells, however the timing and stimulatory requirements for generating optimal Th1 responses have not been carefully examined. We used antibiotic interruption of vaccination with live attenuated Salmonella to examine the requirements for Salmonella-specific Th1 development and protective immunity. Optimal development of protective immunity to Salmonella infection required at least one week of exposure to the live attenuated Salmonella strain. In contrast, optimal development of Salmonella-specific Th1 cells required two weeks of in vivo colonization. Thus, sustained in vivo stimulation with a live vaccine strain is essential for the development of robust Salmonella-specific Th1 cells.