If you have ever spent time house-hunting, it is likely that you will have heard the old adage — location is everything. The same principle applies to the immune system. Now, reporting in Immunity, McSorley et al. show that T-cell responses to Salmonella in mice are limited to mucosal sites, despite the existence of a disseminated infection.

Salmonella bacteria can cause a range of symptoms, from food poisoning to typhoid fever. Mouse models of infection have been valuable for our understanding of the immune response to Salmonella, but several questions remain unanswered. For example, it is not clear where naive Salmonella-specific T cells first encounter antigen or whether these T cells migrate to the liver, which is one of the main sites of infection. To address such questions, McSorley and colleagues developed an adoptive transfer system, which permits the tracking of Salmonella-specific CD4+ T cells in vivo. Transgenic Salmonella-specific SM1 T cells were transferred into congenic wildtype mice; this mimics the natural situation in which Salmonella-specific T cells compete with T cells of other specificities. Differences in the expression of CD90 alleles between donor and host enabled the tracking of donor T cells in the recipient mice.

McSorley et al. found that SM1 T cells in the Peyer's patches responded to Salmonella bacteria within three hours of oral infection. The rapidity of this response indicates that it is not necessary for antigen-presenting cells (APCs) to migrate to the mesenteric lymph nodes to initiate T-cell responses; rather, it seems that dendritic cells in the Peyer's patches can acquire antigen rapidly and stimulate nearby T cells. The clonal expansion of SM1 T cells was restricted to mucosal lymphoid tissues, despite the presence of bacterial infection in other organs, such as the spleen and liver. The authors speculate that splenic SM1 T cells are unresponsive because APCs and T cells are anatomically separated in the spleen — preliminary data show that bacteria are located in the red pulp and T cells in the white pulp early after infection. But, an alternative explanation (see Further Reading) is that although the bacterial load in the spleen is high, the antigenic load might be low. SM1 T cells are specific for a flagellin epitope, and the expression of flagellin in systemic bacteria, which can switch off expression of certain genes, might be lower than in mucosal bacteria.