DCs redirect T cell traffic

Dendritic cells (DCs) are the master regulators of T cell recirculation, according to a study by Mora et al. on page 303. Memory T cells—thought to be programmed to return to the location in which they first encountered antigen—can be rerouted by an encounter with a DC from another location.Previous studies have shown that memory T cells express a characteristic array of adhesion molecules and chemokine receptors on their surface that reflect the location of activation and direct their trafficking back to that site. Recently, this group showed that gut DCs, but not spleen or peripheral lymph node DCs, induced the up-regulation of the gut-homing integrin α4β7 on T cells.

Mora et al. now show that these “committed” T cells are not set in their ways. In vitro, T cells stimulated with skin-derived DCs and later restimulated with gut-derived DCs quickly replaced their skin-homing molecules with the gut-homing variety (and vice versa), demonstrating that recirculating T cells simply obey the signals provided by the most recently encountered DC. In vivo, tissue-specific effector–memory T cells can revert to central–memory status, thus acquiring the capacity to home to a variety of second lymphoid tissue where they can encounter new instructions from resident DCs.

This plasticity may be important, points out senior author Ulrich von Andrian, as it would allow the immune system to fight off pathogens that can colonize more than one site. It might also provide a new approach to treating T cell–mediated inflammatory diseases, if harmful T cells can be diverted to an innocuous site.