Patients infected by Leishmania braziliensis develop debilitating skin lesions . The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known . Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4 + and CD8 + T cell subsets . Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls . The proportions PD1 +, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments . Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro . While we previously showed a significant correlation between the accumulation of senescent CD8 + CD45RA + CD27 - T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology . Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood . Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis.
Index: Leishmania braziliensis, PD-1, T cell exhaustion, cutaneous leishmaniasis, immunosenescence, inhibitory checkpoint receptors, senescent T cells