Increased numbers of NK cells, NKT-like cells, and NK inhibitory receptors in peripheral blood of patients with chronic obstructive pulmonary disease

Abstract

T cells and B cells participate in the pathogenesis of COPD. Currently, NK cells and NKT cells have gained increasing attention. In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS) were recruited, and their pulmonary function was assessed. The frequencies of CD3(+) T, CD4(+) T, CD8(+) T, B, NK, and NKT-like cells were determined using flow cytometry. The frequencies of spontaneous and inducible IFN- γ (+) or CD107a(+) NK and NKT-like cells as well as activating or inhibitory receptors were also detected. The potential association of lymphocyte subsets with disease severity was further analyzed. Significantly decreased numbers of CD3(+) and CD4(+) T cells, and the CD4(+)/CD8(+) ratio, but increased numbers of CD3(-)CD56(+) NK and CD3(+)CD56(+) NKT-like cells were observed in COPD patients compared to HNS. The frequencies of inducible IFN- γ -secreting NK and NKT-like cells were less in COPD patients. The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater. The frequency of CD158b(+) NK cells was negatively correlated with FEV1% prediction and FEV1/FVC. Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD.

Figure 1

Lymphocyte subsets in COPD patients and HNS. (a) The cells were gated initially on living lymphocytes. At least 50,000 events were analyzed for each sample. Viable lymphocytes were gated on the basis of forward and side angle light scattering characteristics. Data shown are representative charts from different groups of subjects and the frequencies of CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, NK cells, and NKT-like cells in individual subjects. (b), (c), (d), (e), and (f) Summarized data show the number of CD3⁺ T cells, CD3⁺ CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁻CD56⁺ NK cells, and CD3⁺CD56⁺ NKT-like cells in COPD patients and HNS. (g) Summarized data show the CD4⁺/CD8⁺ ratio. The horizontal lines show the median.

Figure 2

The frequencies of inducible IFN-γ-secreting NK cells and NKT-like cells and CD107a⁺ NK cells and NKT-like cells in COPD patients and HNS. (a) and (b) The cells were gated initially on CD3⁻CD56⁺ NK cells. At least 10,000 events were analyzed for each sample. Data shown are representative charts from different groups of subjects and the frequencies of IFN-γ-secreting NK cells and CD107a⁺ NK cells in individual subjects. (c) and (d) The cells were gated initially on CD3⁺CD56⁺ NK cells. Data shown are representative charts from different groups of subjects and the frequencies of IFN-γ-secreting NKT-like cells and CD107a⁺ NKT-like cells in individual subjects. (e) and (f) Summarized data show the frequency of IFN-γ-secreting NK cells and CD107a⁺ NK cells in individual subjects. (g) and (h) Summarized data show the frequency of IFN-γ-secreting NKT-like cells and CD107a⁺ NKT-like cells in individual subjects.

Figure 3

CD158a⁺ NK cells, CD158b⁺ NK cells, and CD158b⁺ NKT-like cells in COPD patients. (a) Data shown are representative charts from different groups of subjects and the frequencies of CD158a⁺, CD158b⁺ NK cells, and CD158b⁺ NKT-like cells in individual subjects. (b) Summarized data show the number of CD158a⁺ NK cells in COPD patients and HNS. The horizontal lines show the median. (c) Summarized data show the number of CD158b⁺ NK cells in COPD patients and HNS. (d) Summarized data show the number of CD158b⁺ NKT-like cells in COPD patients and HNS.

Figure 4

The correlation between FEV₁, FEV₁/FVC ratio and the frequency of CD158b⁺ NK cells in COPD patients. (a) The correlation between FEV₁ and the frequency of CD158b⁺ NK cells. (b) The correlation between the FEV₁/FVC ratio and the frequency of CD158b⁺ NK cells.