T cell receptor repertoire of T lymphocytes recovered from the lung and blood of patients with sarcoidosis.
We evaluated the repertoire of V beta segments used in forming the T-cell receptor of lavage and blood T lymphocytes from 11 sarcoid patients and 10 normal subjects using procedures based on quantitative polymerase chain reaction, permitting analysis of both the abundance of transcripts using each of 20 different V beta families and the diversity of the VDJC beta rearrangements within each V beta family. Blood and lung T cells from sarcoid patients had a very diverse V beta repertoire. For all V beta families but one, the abundance of the V beta transcripts fell within the mean +/- 2 SD of that observed for normal blood lymphocytes; no difference in the overall abundance was observed comparing lavage and blood T cells, and the length of VDJC beta rearrangements for a given V beta family in samples from sarcoid patients was usually quite heterogeneous. Despite the overall polyclonality, evidence for selective expansion of T cells was found, in that an increased abundance of V beta 19 transcripts was observed for sarcoid blood and/or lung T cells in eight out of 11 patients studied, and rearrangements of a single predominant length using certain (e.g., V beta 19, V beta 14), but not all, V beta families were present. Sequencing confirmed the presence of a single predominant VDJC beta rearrangement in these cases. These findings suggest that the alveolitis in sarcoidosis results from two distinct processes, a local clonal expansion of T cells associated with an apparently nonspecific accumulation of T cells with an extremely diverse V beta repertoire.
Bellocq
A
A
INSERM U.82, Faculté de Médecine Xavier Bichat, Paris, France.
Lecossier
D
D
Pierre-Audigier
C
C
Tazi
A
A
Valeyre
D
D
Hance
A J
AJ
D000328:Adult; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D017565:Sarcoidosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D013601:T-Lymphocytes / Q000737:chemistry*
D016693:Receptors, Antigen, T-Cell, alpha-beta