PD-L1 May Mediate T-Cell Exhaustion in a Case of Early Diffuse Leishmaniasis Caused by (L.) .

Introduction: Diffuse cutaneous leishmaniasis (DCL) is a rare disease form associated with (L.) in South America. It represents the "anergic" pole of American Tegumentary Leishmaniasis, and the explanation for its resistance to treatment remains elusive. We aimed to study some possible immunological mechanisms involved in the poor DCL treatment response by evaluating some cell surface molecules obtained from a patient with DCL by flow cytometry.

Case Presentation: A 65-year-old DCL patient who initially failed to respond to the standard treatment for the disease showed vacuolated macrophages filled with amastigotes in lesion biopsy, and . (L.) was identified through ITS1PCR amplification. The skin test and indirect immunofluorescence analysis revealed negative results. Peripheral blood from the patient was collected after a few months of treatment, when the patient presented with no lesion. Peripheral blood mononuclear cells were analyzed and after 48 h of stimulation with soluble . (L.) antigen (SLA). Cell death, surface molecules, and intracellular molecules, such as IFN-γ and granzyme B, were analyzed in the cells using flow cytometry. Analysis of the surface markers showed an increased expression of the inhibitory molecule programmed death ligand 1 (PD-L1) in the monocytes restimulated with SLA (approximately 65%), whereas the negative controls were 35% positive for PD-L1. Conversely, compared with the negative controls, we observed a decrease in CD4IFN-γ T cells (8.32 versus 1.7%) and CD8IFN-γ T cells (14% versus 1%). We also observed a relevant decrease in the granzyme B levels in the CD8 T cells, from 31% in the negative controls to 5% after SLA restimulation.

Conclusion: The dysfunctional activation of PD-L1 inhibitory pathway after antigen stimulation and reduced levels of IFN-gamma and granzyme B-producing cells could be closely related to unresponssiveness to standard drug treatment of DCL patient.