Background: Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4⁺, CD8⁺, and CD19⁺ cells. Results: IL-27 stimulation significantly increased TIM-3 expression on CD8⁺ T cells (2.18 ± 0.32% vs. 3.09 ± 0.49%, p = 0.009), a hallmark of T cell exhaustion. IL-27 also modestly increased intracellular Gal-9 levels in total lymphocytes (93.91 ± 1.17% vs. 96.55 ± 0.67%, p = 0.005). Additionally, IL-27 reduced CD4⁺ T cell proportions (26.71 ± 4.19% vs. 22.01 ± 3.23%, p = 0.010). Although numerically modest, these changes may be biologically pertinent in the context of checkpoint-mediated CD8⁺ T-cell exhaustion. Conclusions: IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study.

Background: It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) reflects the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. In this study, we aimed to assess the prognostic value of the BAL cytoimmunologic profile in PCS-related ILD. Materials and Methods: We enrolled 58 non-smoking patients with a history of COVID-19 and new-onset ILD, divided into PCS remission and PCS persistence groups based on clinical data, including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1), and markers of Th1/Th2/Th17 polarization. Results: The PCS groups compared to the control showed increased total cell, lymphocyte, and neutrophil counts and a high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to the controls presented an increased neutrophil count (26 [17–36] vs. 2.6 [1.9–5.4] 103/mL, median [Q1–Q3], p < 0.001) and percentage, BAL NLR (0.77 [0.26–1.63] vs. 0.21 [0.17–0.31], p < 0.0001), CD8+PD1+ cell percentage (43.5 [34–60.5] vs. 24.5 [22–44]%, p = 0.045), and a decreased CD4:CD8 ratio. A high percentage of CD4+CD196+CD183 cells (relevant to Th17 activity, 6.2 [2.0–9.4] vs. 1.2 [0.7–2.7]%, p = 0.02) and increased BAL supernatant elevated IL-8 levels (62.5 [16–243] vs. 10.9 [3.44–32] pg/mL, p = 0.002) were found in the PCS persistence vs. control groups. In the total PCS group, predicted values of Vital Capacity (VC) [16–243] and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR; VC correlated negatively with BAL CD8+PD1+; and DLCO correlated positively with the CD4:CD8 ratio. Conclusions: Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, an elevated percentage of CD8+PD1+ lymphocytes, and a decline in the CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence.

Background. It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) may reflect the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. We aimed to assess the prognostic value of BAL cytoimmunologic profile in PCS-related ILD. Material & Methods. We enrolled 58 non-smoking patients with COVID-19 history, having new-onset ILD, divided into PCS remission and PCS persistence groups, based on clinical data including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1) and markers of Th1/Th2/Th17 polarization. Results. PCS compared to controls showed increased total cell, lymphocyte and neutrophil count and high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to controls presented increased neutrophil count (26[17-36] vs. 2.6[1.9-5.4] 10³/ml, median[Q1-Q3], p<0.001 ) and percentage, BAL NLR (0.77[0.26-1.63] vs. 0.21[0.17-0.31], p<0.0001) , CD8+PD1+ cell percentage (43.5 [34-60.5] vs. 24.5[22-44]%, p=0.045), decreased CD4:CD8 ratio. High percentage of CD4+CD196+CD183- cells (relevant to Th17 activity, 6.2[2.0-9.4] vs 1.2[0.7-2.7]%, p=0.02 ), and increased BAL supernatant elevated IL-8 levels (62.5[16-243] vs. 10.9[3.44-32]pg/mL, p=0.002) were found in PCS persistence vs. controls. In total PCS, predicted values of Vital Capacity (VC) and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR, VC correlated negatively with BAL CD8+PD1+; DLCO correlated positively with CD4:CD8 ratio. Conslusions. Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, elevated percentage of CD8+PD1+ lymphocytes, decline in CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence.