Humanised Mice in Cutaneous Leishmaniasis—T‐Cell Recruitment Into Human Skin Transplants After <scp><i>Leishmania major</i></scp> Infection

Treatment against leishmaniasis is associated with severe side effects, high costs, and parasitic resistance. Preclinical models such as humanised mice would aid therapeutic improvement or the development of a vaccine. We developed a model in which human skin transplants on immunodeficient mice are infected with Leishmania major. Parasite inoculation of the skin transplant led to a robust infection with increasing numbers of parasites in the skin and visceral organs. In addition, intraperitoneally co-administered allogeneic peripheral blood mononuclear cells (PBMCs) were strongly recruited to skin lesions, with ≥ 65% of the cells being positive for anti-human CD45; we identified ~20% CD4⁺ and ~50% CD8⁺ human T cells. The number of skin-resident macrophages or dendritic cells was unaltered compared to healthy skin prior to transplantation, and PBMC administration did not alter their numbers. Together, we show that parasitic infection provides a strong inflammatory signal that leads to recruitment of T cells into skin transplants. The presence of antigen-presenting cells in the transplants-as an important prerequisite for proper APC-T-cell interaction-recreates a fully human skin microenvironment that allows for stroma/immune cell interactions upon infection. This model may be of high interest to researchers interested in translating skin research questions into the human system in vivo.