Long-Lived Skin-Resident Memory T Cells Contribute to Concomitant Immunity in Cutaneous Leishmaniasis

Memory T cells, which protect against reinfection in many diseases, have predominantly been characterized in models of acute viral or bacterial infection. In contrast, memory T cells are less well understood in diseases where pathogens persist following disease resolution, such as leishmaniasis, in spite of the fact that these infections often lead to immunity to reinfection, termed concomitant immunity. Defining the T cells that mediate concomitant immunity is an important step in developing vaccines for these diseases. One set of protective T cells are short-lived effector T cells requiring constant stimulation, which would be difficult to maintain by vaccination. However, parasite-independent memory T cells, including central memory T cells (Tcm) and skin-resident T cells (Trm) have recently been described in leishmaniasis. Given their location, Trm cells are particularly suited for protection, and were found to globally seed the skin following Leishmania infection or immunization. Upon challenge, Trm cells rapidly respond to reduce the parasite burden, suggesting that developing strategies to generate parasite-independent Trm cells will be an important step in the quest for a successful leishmaniasis vaccine.