Oligoclonal V gene usage by T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients.
The T-cell antigen receptor (TCR) repertoire was examined in lymphocytes isolated from the lungs and blood of 12 sarcoidosis patients and nine control patients. This analysis, by polymerase chain reaction (PCR), examined the variable (V)-domain genes of both the alpha and beta chains of the TCR. This is the first study to examine the usage of all known V alpha gene segments in sarcoidosis. A similar degree of diversity was observed in the TCR repertoire in the lungs and blood of the sarcoidosis patients. However, 11 of the 12 sarcoidosis patients showed an increased use of particular TCR V alpha and V beta genes in lung T cells as compared with blood. The pattern of TCR V gene bias in the lung T cells was specific for each patient. The clonality of selected V genes was examined by determining the third complementarity-determining region (CDR3) length polymorphism of particular PCR products. The majority of lung T cells with biased TCR V gene segments were oligoclonal. Altogether, these results suggest oligoclonal expansion of lung T cells in response to a local antigenic stimulus, with additional nonspecific T-cell accumulation. The variability in the V gene segments used by the expanded T-cell subsets in different sarcoidosis patients may reflect different epitopes or antigens being recognized in the lung, as well as variations in major histocompatibility complex (MHC) haplotype between the patients.
Jones
C M
CM
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Lake
R A
RA
Wijeyekoon
J B
JB
Mitchell
D M
DM
du Bois
R M
RM
O'Hehir
R E
RE
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D017931:DNA Primers; D015342:DNA Probes; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D012129:Respiratory Function Tests; D012507:Sarcoidosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D012907:Smoking; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D015342:DNA Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta