Clonal expansion of lung V delta 1+ T cells in pulmonary sarcoidosis.

Abstract

Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for y/6 T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular 'y/6 T cell receptors. An abnormally high percentage of 'y/6 cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing a/, receptors. Furthermore, as in normals, the circulating 'y/6 cells in patients predominantly expressed V-y9 /V52 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of 7a/6 cells expressing VS1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V1 + cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus. (J. Clin. Invest. 1993. 91:292-300.)

Evidence for Mycobacteria in Sarcoidosis

“…It is probable that distinct antigens can precipitate sarcoidosis or sarcoidosis-like diseases in susceptible individuals. An antigen-driven process is also consistent with the oligoclonal restriction of CD41 T cells seen in sarcoidal granulomas (15)(16)(17).…”

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

“…In addition, many examples of clonal T-cell expansion in tumorinfiltrating lymphocytes in patients with tumors and autoimmune diseases have been reported (58 -60). Furthermore, clonal expansion of T/␥␦-lymphocytes has been reported to occur in granulomatous diseases such as sarcoidosis and tuberculosis, and some of our cases (data not shown) fell in this category (61,62). Conversely, the failure to detect a clonal population in an immunomorphological and clinical context highly suggestive of a malignant process (in approximately 10 -20% of malignant lymphoid proliferations) should be interpreted with caution.…”

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

“…One further study demonstrated a restricted V/~I repertoire in the peripheral blood of certain patients with rheumatoid arthritis but not in four healthy controls (30). However, it is worth noting that a recent report of preferential Vis1-J81 junctional repertoires in sarcoidosis, demonstrated a repetitive sequence in cDNA from the PBL of one of the normal control (31).…”

“…In the present work, we have shown that V81-J81junctions, while displaying the extensive alterations of germline sequences that are characteristic of post fetal stages (14), are not randomly represented among PBL V/$1 + cells in a large fraction of healthy donors. The description of such repeated sequences in the PBL of healthy donors is unprecedented since only a few V81-J81 sequences have been published to date (28)(29)(30)(31). Two studies showed an unrestricted repertoire in PBL from patients and normal controls, but predominant sequences in acute multiple sclerosis (29) and leprosy lesions (28), respectively, suggesting in situ selection of particular VIS1 + cells by so far undefined antigens.…”