Tissue-resident memory CD8+ T cells shape secondary T cell responses

Tissue-resident memory CD8+ T (TRM) cells provide effective early protection against local reinfection. TRM cells are non-recirculating memory T cells, which are confined to local tissue sites at the resting state. However, it remains unclear whether TRM cells maintain their strict tissue confinement after reinfection. This is an important issue, given that memory T cells shape secondary T cell responses upon pathogen reencounter. To examine TRM responses, we have developed a unique lineage tracer mouse model, which exploits the TRM-defining transcription factor Hobit to fate-map the progeny of TRM cells in secondary responses. After reinfection, a sizeable fraction of secondary memory T cells developed downstream of TRM cells. Phenotypically, these tissue-experienced memory cells shared properties with the effector memory (TEM) population, including expression of KLRG1 and lack of CD62L expression, presence in the spleen and circulation, and absence from lymph nodes. However, secondary TEM cells developing from TRM cells also displayed transcriptionally and functionally distinct properties from other secondary TEM cells.