LIMITED HETEROGENEITY OF BIASED T-CELL RECEPTOR V-BETA GENE USAGE IN LUNG BUT NOT BLOOD T-CELLS IN ACTIVE PULMONARY SARCOIDOSIS

Sarcoidosis is a multisystem disorder characterized by non-caseating g ranulomas and the accumulation of CD4(+) T cells in involved tissues s uch as the lung. To evaluate the diversity of the CD4(+) T-cell repert oire in this disorder, a detailed clonal analysis was performed in fiv e individuals with active sarcoidosis who demonstrated preferential ac cumulation of T cells expressing the T-cell receptor variable gene fam ily V beta 8 in either the lung or blood. In three individuals, analys is of unselected samples of nucleotide sequences derived from V beta 8 (+) lung T cells demonstrated degrees of clonality ranging from 11% to 46%, indicating the expansion of limited numbers of V beta 8(+) T-cel l clones in the lung. Analysis of the corresponding deduced amino acid sequences demonstrated common VDJ junctional amino acid residues in t he dominant V beta 8(+) T-cell clones derived from two oligoclonal V b eta 8(+) lung T-cell populations, consistent with an antigen-specific T-cell response. In contrast, analysis of V beta 8(+) CD4(+) T cells f rom the blood of an individual with a marked bias for peripheral blood V beta 8(+) T cells demonstrated no evidence of oligoclonality, sugge sting that the stimulus for circulating biased V beta-specific T cells in sarcoidosis may derive from a different, perhaps superantigenic, o rigin. Clinical improvement in the disease either in response to treat ment with corticosteroids or as a result of spontaneous resolution was associated with a decrease in the proportion of V beta 8-specific T c ells in the biased lung and/or blood T-cell compartments. Together, th ese observations are consistent with a role for this T-cell subset in the clinical manifestations of active granulomatous disease.