Am. J. Respir. Cell Mol. Biol., Vol 14, No. 5, 05 1996, 470-477.
Oligoclonal V gene usage by T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients
CM Jones, RA Lake, JB Wijeyekoon, DM Mitchell, RM du Bois and RE O'Hehir
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.
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.
