Chronic infectious diseases are responsible for significant morbidity and mortality. They impose high costs on health systems and promote poverty. Visceral leishmaniasis(VL) is caused by the protozoan parasite Leishmania donovani. Like other chronic infectious diseases, such as malaria, TB and HIV, VL is characterised by immune dysfunction that impairs critical CD4+ T cell responses for parasite control, which in turn can promote persistent infection and associated pathology. CD4+ T cells are integral to disease outcome and we aim to identify CD4+ T cell molecules to target and manipulate to improve outcomes for VL patients. To distinguish CD4+ T cell molecules mediating effective and ineffective anti-parasitic immunity, we examined tissue-specific CD4+ T cell responses using scRNAseq in a model of experimental-VL. In this model, the liver is a site of acute, resolving infection with highly effective anti-parasitic CD4+ T cells (similar to the immune presentation of asymptomatic humans), while the spleen is a site of chronic infection and ineffective CD4+ T cells (similar to the immune presentation in VL patients). To study and track CD4+ T cell responses in experimental-VL, we employed CD4+ T cell receptor (TCR) transgenic cells that are specific for a Leishmania antigen (PEPCK). We also employed a Leishmania-specific MHC-class II I-Ab tetramer (PEPCK335-351) to examine the entire complexity of the CD4+ T cell response encompassing a spectrum of TCR specificities. To determine how drug treatment modulates CD4+ T cell responses, a group of mice were also treated with a single dose of AmBisome (current treatment for VL patients). PEPCK and PEPCK335-351-positive cells were sorted from the liver and spleens of control- or AmBisome- treated mice at various time points throughout infection and subjected to scRNAseq using the 10x Genomics Chromium platform and the 5’ reagent kit. Analysis of this data set will be presented.