T cell receptor repertoire of T lymphocytes recovered from the lung and blood of patients with sarcoidosis

Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):646-54. doi: 10.1164/ajrccm.149.3.7906994.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / cytology*
  • Case-Control Studies
  • Female
  • Gene Expression
  • Gene Rearrangement
  • Humans
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Sarcoidosis, Pulmonary / blood*
  • Sarcoidosis, Pulmonary / diagnosis
  • Sarcoidosis, Pulmonary / pathology*
  • T-Lymphocytes / chemistry*

Substances

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