Increased γ/δ-positive T-cells in blood and bronchoalveolar lavage of patients with sarcoidosis and hypersensitivity pneumonitis

Abstract

A small population of T-cells does not express the conventional T-cell receptor (TCR), characterized by the α and β polypeptide chains (α/β TCR) but two polypeptides termed γ and δ (γ/δTCR). Changes in γ/δTCR expression may be relevant as the cause or consequence of several diseases. Our study was undertaken to determine and compare the distribution of T- cells expressing γ/δTCR in blood and bronchoalveolar lavage (BAL) of patients with sarcoidosis, hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), and of healthy controls. In addition, the association between γ/δTCR of blood T-lymphocytes and accessory molecules was analysed. Using direct immunofluorescence with the anti-γ/δTCR and anti-CD3 monoclonal antibodies (MoAbs) followed by flow cytometric analysis, the blood of patients with pulmonary sarcoidosis, HP, IPF and of healthy controls was analysed. To reveal the association between γ/δTCR of blood T- lymphocytes and the accessory molecules, expression of CD4, CD8 and CD25 were determined. Calculating the percentage and the total number of CD3+ γ/δTCR cells in blood, the data indicated a significant increase of γ/δT-cells in individuals with pulmonary sarcoidosis and HP, compared to healthy controls and IPF patients. In sarcoidosis patients with elevated CD3+ γ/δTCR levels, significantly lower CD4/CD8 ratios were observed. In addition, our data demonstrate a correlation between the decrease of CD4+ cells in blood and the amplified appearance of γ/δTCR expression in sarcoidosis patients, but not in HP patients. γ/δTCR+ cells were either CD8-positive (approximately 50%), or had a 'double-negative phenotype' (CD4-/CD8-) (remaining 50%). Circulating blood γ/δT-cells were CD25-negative, suggesting a lack of activation. The total number of CD3+ γ/δTCR+-bearing lymphocytes in BAL fluid was increased in sarcoidosis and HP, compared with IPF. A corresponding increase of CD3+ γ/δTCR+ cells was observed in blood and BAL of sarcoidosis patients. In conclusion, our data indicate that levels of γ/δT-cells are increased in blood and BAL fluid of patients with sarcoidosis and HP. Although this suggests a pathogenetic role for γ/δTCR, it is not clear whether its expression is a causal factor, or a consequence, of these diseases.