Selective activation and accumulation of oligoclonal V beta-specific T cells in active pulmonary sarcoidosis.
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.
Forman
J D
JD
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Klein
J T
JT
Silver
R F
RF
Liu
M C
MC
Greenlee
B M
BM
Moller
D R
DR
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics*; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta