OLIGOCLONAL-V GENE USAGE BY T-LYMPHOCYTES IN BRONCHOALVEOLAR LAVAGE FLUID FROM SARCOIDOSIS PATIENTS

The T-cell antigen receptor (TCR) repertoire was examined in lymphocyt es isolated from the lungs and blood of 12 sarcoidosis patients and ni ne control patients. This analysis, by polymerase chain reaction (PCR) , examined the variable (V)-domain genes of both the alpha and beta ch ains of the TCR. This is the first study to examine the usage of all k nown V alpha gene segments in sarcoidosis. A similar degree of diversi ty was observed in the TCR repertoire in the lungs and blood of the sa rcoidosis 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 lu ng T cells was specific for each patient. The clonality of selected V genes was examined by determining the third complementarity-determinin g region (CDR3) length polymorphism of particular PCR products. The ma jority of lung T cells with biased TCR V gene segments were oligoclona l. Altogether, these results suggest oligoclonal expansion of lung T c ells in response to a local antigenic stimulus, with additional nonspe cific 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, a s well as variations in major histocompatibility complex (MHC) haploty pe between the patients.