Revisiting the past in light of current knowledge on γδ T cells in leishmaniasis

Leishmaniasis, a group of neglected diseases caused by Leishmania parasites, presents complex immune responses shaped by parasite strain, disease type, treatment regimens, and experimental models. Among the immune players, γδ T cells have gained significant attention due to their dual role in producing pro-inflammatory cytokines like Interleukin (IL)-17 and Interferon (IFN)-γ, alongside their cytotoxic functions. These cells play pivotal roles in various diseases, including cancer and malaria, and their impact on leishmaniasis is increasingly recognized. Since their identification in patient lesions in 1989, γδ T cells have been shown to influence disease progression in leishmaniasis. However, their role remains nuanced, with a delicate balance between IL-17, IL-10, and IFN-γ production, each cytokine modulating the expression of others. In this review, we explore how γδ T cells shape the course of leishmaniasis in humans, affecting both disease outcomes and treatment responses. We also highlight significant differences between species and experimental models, which critically impact infection dynamics. Furthermore, we emphasize probable ligands present on Leishmania parasites that may activate γδ T cells, providing insights into potential mechanisms of immune recognition and response. Additionally, we examine the sublocalization of γδ T cells across various tissues, providing a detailed view of their distribution in the context of leishmaniasis. These insights raise crucial considerations for advancing disease control strategies and the development of innovative therapeutic approaches.