T-lymphocytes and cytokines in sarcoidosis

Abstract

In the last few years, a number of reports have clearly shown that pulmonary T lymphocytes have evolved a number of effector mechanisms to respond to foreign antigens, ranging from direct cytotoxicity mechanisms to secretion of lymphokines, that have the ability to activate themselves or other pulmonary immunocompetent cells. Furthermore, there is also evidence that lung T cells may have a role in the immunopathogenetic mechanisms taking place in the lung of most immune-mediated diffuse lung disorders. In this paper, we will review the current concepts on the recruitment, homing, and activity of T lymphocytes in the lower respiratory tract of patients with sarcoidosis. The relevant phenotypic and functional abnormalities detected on T cells in sarcoidosis will be discussed. Furthermore, we will comment recent findings on the ability of immunomodulatory molecules, such as proinflammatory cytokines, chemokines, and other cytokines, to regulate T-cell function in immune mechanisms leading to granuloma formation and maintenance.

The role of inflammation and antiinflammation therapies in keratoconjunctivitis sicca

“…36 Another important fi nding is the increased levels of proinfl ammatory cytokines such as tumor necrosis factor-α (TNFα) in sarcoidosis. 37,38 TNFα exerts its effect by binding to specifi c cell surface receptors such as membrane TNF receptor (mTNFR)-1 and mTNFR-2, and can be blocked by soluble TNF receptor (sTNFR)-1 and sTNFR-2. 39 Because of these properties, in the past several years, both TNFα monoclonal antibody and soluble TNF receptor have been investigated for the treatment of sarcoidosis, and ocular involvement as well.…”

Corticosteroid treatment in sarcoidosis

“…A number of considerations are currently fundamental to the understanding of sarcoidosis: 1) the disease is defined by the presence of granulomas, rarely with caseation but often with fibrinoid necrosis [3]; 2) sites of granulomatous inflammation contain variable numbers of activated T-cells and cells from the monocyte/macrophage lineage [4,5]; 3) these T-cells, macrophages and other local tissue cells express many pro-inflammatory cytokines and chemokines that have been shown experimentally to be critical in cell-mediated immune responses and granuloma formation, with a role for transforming growth factor-b in spontaneous resolution of granulomas [6][7][8]; 4) sarcoidosis is associated with a T-helper cell type 1 immune response, at least in the initial years of disease [9]; 5) T-cell expansion is oligoclonal, consistent with an antigen-driven immune response [10,11]; 6) multiple aetiological agents have been suggested to initiate this response, e.g. exposure to specific microorganisms such as Propionibacterium acnes, but no causation has been established to date [12]; 7) recently, evidence has been found for a loss of immunoregulation by CD1d-restricted natural killer T-cells and a genetically determined dysfunction of a putative co-stimulatory molecule (butyrophilin-like protein 2) [13,14]; and 8) Lö fgren's syndrome, the subset of sarcoidosis with the best prognosis, is associated with the formation of circulating immune complexes and specific human leukocyte antigen and nonhuman leukocyte antigen genotypes essentially 100% of the time [15][16][17].…”

Intramedullary spinal sarcoidosis: clinical improvement reflected in T-lymphocyte subpopulation ratios

“…In pulmonary sarcoidosis, the T4:T8 ratio of bronchoalveolar fluid mirrors treatment response. 2 Nonimprovement of the T4:T8 ratio with cyclosporine proved lack of benefit of that drug in pulmonary sarcoid. 7 In our patient, post-treatment T4:T8 ratio reflected his clinical picture with considerable improvement.…”

“…1 In contrast, pulmonary sarcoidosis has characteristic immunocytologic changes in alveolar fluid. 2 Small studies suggest an elevated ratio of CSF CD4:CD8 þ (T helper:T suppressor or T4:T8) lymphocytes in neurosarcoidosis. 3 We present a patient with sarcoid myelopathy whose clinical and radiographic diagnosis and treatment response correlated with the CSF immune profile.…”