Expansion of Pulmonary CD8+CD56+ Natural Killer T-Cells in Hypersensitivity Pneumonitis

Abstract

Natural killer T (NKT) cells, a newly identified subgroup of T cells with immunoregulatory function, may be implicated in the pathogenesis of interstitial lung disease (ILD). We used multiparameter flow cytometry with antibodies to CD3, CD4, CD8, CD14, CD19, CD45, CD16/56, CD56, CD161, and Valpha24 invariant T-cell receptor (TCR) in BAL fluid (BALF) to examine the frequency and distribution of pulmonary NKT cells in several cases of ILD. We included 57 patients with sarcoidosis and 17 patients with hypersensitivity pneumonitis. We found significantly higher frequencies of pulmonary NKT cells in patients with hypersensitivity pneumonitis in comparison to the other study patients with ILD (median proportion of NKT cells, 11%; range, 3 to 38%; vs 3%; range, 0 to 16%; p < 0.0001). In contrast, there was no difference in the proportion of conventional natural killer cells. We found that a major subset of NKT cells in the BALF of patients with hypersensitivity pneumonitis was a CD8+CD56+ population that did not express the invariant TCR. These results suggest the involvement of NKT cells in the pathogenesis of hypersensitivity pneumonitis.