Step-by-step: the CD8 T cell journey in leishmaniasis

Leishmaniasis is a group of vector-borne diseases caused by protozoan parasites of the genus Leishmania that affect millions of people across nearly 100 countries. Clinical presentations range from self-resolving cutaneous ulcers to life-threatening visceral disease, depending on the infecting species and host immune response. While CD4 T cells have long been recognized as central to parasite control, CD8 T cells also play an important role in disease. In this mini-review, we explore the many steps involved in CD8 T cell responses in leishmaniasis, with a focus on antigen recognition, recruitment, effector function, memory development, and dysfunction. Drawing on both murine models and human studies, we highlight the duality of CD8 T cells, which can contribute to protection but also drive immune-mediated tissue damage. Recent advances in transcriptomics, in vivo modeling, and immunophenotyping have begun to clarify the conditions under which CD8 T cells support vs hinder host defense. Despite this progress, critical questions remain, and continued investigation into the heterogeneity and regulation of CD8 T cells in leishmaniasis promises not only to deepen our understanding of host-pathogen interactions but also to guide the development of targeted immunotherapies and vaccines.