Selective activation and accumulation of oligoclonal V beta-specific T cells in active pulmonary sarcoidosis.

Abstract

Sarcoidosis is a granulomatous disease in which activated T cells, responding to an unidentified stimulus, accumulate at sites of disease such as the lung. To evaluate the hypothesis that active sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR) specific T cells, we analyzed TCR VB gene expression in lung and blood T cells of patients with active sarcoidosis and, for comparison, normal individuals using polymerase chain reaction amplification of 20 VB gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR V,8 distributions similar to that of normal blood, providing evidence for a lack of generalized skewing of the T cell repertoire in the normal, noninfected lung. Compared to normnal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more Vfi genes in either the lung or blood. Five Vfi gene families (Vfi5, Vp8, Vfi15, Vfi16, and V1318) were most frequently utilized in a biased fashion by sarcoid lung or blood T cells. Furthermore, dramatic skewing of the T cell repertoire was apparent when sarcoid lung and blood T cells were expanded by short-term culture with IL-2. Sequence analysis demonstrated a bias in V,3 gene expression was usually due to expansion of select VB-specific clones, some of which contained a similar V(D)J junctional region motif. These observations provide evidence for a selective activation and accumulation of antigen-specific Vf8-expressing T cells in sarcoidosis. (J. Clin. Invest. 1994Invest. . 94:1533Invest. -1542

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).…”

Sarcoidosis: immunopathogenetic concepts and their clinical application

“…This observation has been extended to show restricted usage of TCR V α [150], V β [151] and C β -chains [152] in BAL and lung parenchyma [153]. However, no clear distinction between polyclonal and oligoclonal T-cell proliferation in sarcoidosis could be made.…”

T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis

“…In sarcoidosis, characteristic lung accumulations of T-cells expressing distinct TCR Vα or Vβ genes suggest the presence of specific antigens [2][3][4]. Lung-compartmentalised CD4 + T-cells are highly activated [5] and produce T-helper (Th) type 1 cytokines [6,7].…”