Immune-Checkpoint Expression on CD4, CD8 and NK Cells in Blood, Bronchoalveolar Lavage and Lymph Nodes of Sarcoidosis.

Background: Sarcoidosis features non-necrotizing granulomas consisting mainly of activated CD4-lymphocytes. T-cell activation is regulated by immune checkpoint (IC) molecules. The present study aimed to compare IC expression on CD4, CD8 and NK cells from peripheral, alveolar and lung-draining lymph node (LLN) samples of sarcoidosis patients.

Methods: Flow-cytometry analysis was performed to detect IC molecules and a regression decision tree model was constructed to investigate potential binary classifiers for sarcoidosis diagnosis as well as for the IC distribution.

Results: Fourteen patients (7 females) were consecutively recruited in the study; all enrolled patients showed hilo-mediastinal lymph node enlargement and lung parenchyma involvement with chest X-rays and high resolution computed tomography. CD4+PD1+ and CD8+PD1+ were higher in bronchoalveolar lavage (BAL) than in LLN (p = 0.0159 and p = 0.0439, respectively). CD4+ T-cell immunoglobulin and ITIM domain (TIGIT)+ were higher in BAL than in peripheral blood mononuclear cells (PBMCs) (p = 0.0239), while CD8+TIGIT+ were higher in PBMC than in BAL (p = 0.0386). CD56+TIGIT+ were higher in LLN than in PBMC (p = 0.0126). The decision-tree model showed the best clustering cells of PBMC, BAL and LLN: CD56, CD4/CD8 and CD4+TIGIT+ cells. Considering patients and controls, the best subset was CD4+CTLA-4+.

Conclusion: High expression of PD1 and TIGIT on T cells in BAL, as well as CTLA-4 and TIGIT on T cells in LLN, suggest that inhibition of these molecules could be a therapeutic strategy for avoiding the development of chronic inflammation and tissue damage in sarcoidosis patients.