Resident CD4+ T cells accumulate in lymphoid organs after prolonged antigen exposure

Effector and memory CD4+ T cells acquire distinct migratory properties depending on the type and location of the immune responses. Due to the highly dynamic nature of T cell circulation, the comprehensive analysis of these migratory routes requires dedicated experimental approaches. Here, we analyse the migration of effector/memory CD4+ T cells by long-term in vivo cell tracking. We identify a resident population of antigen-experienced CD4+ T cells that resides in lymph nodes and Peyer’s patches without circulation or proliferation. Resident CD4+ T cells constitute up to 50% of all effector/memory cells, including, but not limited to, follicular helper T cells. Furthermore, these non-circulating T cells possess a distinct T cell receptor repertoire and accumulate in Peyer’s patches after continuous oral antigen exposure. Our results provide the first direct evidence for a resident population of effector/memory CD4+ T cells that is retained in lymphoid tissues.