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

J Clin Invest. 1994 Oct;94(4):1533-42. doi: 10.1172/JCI117494.


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 V beta 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 V beta gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR V beta 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 normal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more V beta genes in either the lung or blood. Five V beta gene families (V beta 5, V beta 8, V beta 15, V beta 16, and V beta 18) 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 beta gene expression was usually due to expansion of select V beta-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 V beta-expressing T cells in sarcoidosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / cytology
  • Cells, Cultured
  • Female
  • Gene Expression
  • Genes, Dominant
  • Humans
  • Interleukin-2 / pharmacology
  • Lung / cytology
  • Lymphocyte Activation / physiology*
  • Male
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Sarcoidosis, Pulmonary / immunology*
  • Sequence Analysis, DNA
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*


  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta