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PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis
- Source :
- Frontiers in Immunology, Vol 12 (2021), Frontiers in Immunology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- 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.
- Subjects :
- Adult
Male
lcsh:Immunologic diseases. Allergy
T-Lymphocytes
T cell
Programmed Cell Death 1 Receptor
Population
Immunology
Leishmaniasis, Cutaneous
Leishmania braziliensis
Interferon-gamma
cutaneous leishmaniasis
inhibitory checkpoint receptors
Cutaneous leishmaniasis
T-Lymphocyte Subsets
Immunopathology
PD-1
Humans
Medicine
Immunology and Allergy
Receptor
education
Immune Checkpoint Inhibitors
Original Research
Cell Proliferation
Skin
immunosenescence
Inflammation
T cell exhaustion
education.field_of_study
biology
business.industry
Middle Aged
Immune Checkpoint Proteins
medicine.disease
biology.organism_classification
medicine.anatomical_structure
senescent T cells
Female
Tumor necrosis factor alpha
lcsh:RC581-607
business
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....80a2b0753dbb3998209a832f390aa9df
- Full Text :
- https://doi.org/10.3389/fimmu.2021.632667