BACKGROUND: The role of CD4+ T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8+ cytolytic T cells (CTLs). METHODS: CD8+ CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8+ T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51Cr-release assay. Patients with Löfgren´s syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset. RESULTS: Higher proportions of peripheral CD8+ CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. CONCLUSION: These results demonstrated enhanced peripheral CD8+ CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8+ CTL responses in sarcoidosis.
BACKGROUND: The role of CD4+ T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8+ cytolytic T cells (CTLs). METHODS:CD8+ CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8+ T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51Cr-release assay. Patients with Löfgren´s syndrome (LS) and an acute disease onset, were compared to non-LSpatients with an insidious onset. RESULTS: Higher proportions of peripheral CD8+ CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LSpatients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LSpatients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosispatients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. CONCLUSION: These results demonstrated enhanced peripheral CD8+ CTL responses in sarcoidosis, especially in non-LSpatients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8+ CTL responses in sarcoidosis.
Authors: Michael A Paley; Brandi J Baker; S Richard Dunham; Nicole Linskey; Claudia Cantoni; Kenneth Lee; Lynn M Hassman; Jennifer Laurent; Elisha D O Roberson; David B Clifford; Wayne M Yokoyama Journal: J Neuroimmunol Date: 2022-04-01 Impact factor: 3.221