We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the
protein (flow cytometry) and
mRNA level (RT-PCR) in adult patients with
cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average
HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del homozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had
HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ(group1)) and 36 below (average 1.24 ΔMnI, CF-DQ(group2)). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of
HLA-DQ for the CF-DQ(group2) patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro
HLA-DQ expression was dramatically decreased to background levels in CF-DQ(group2). MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQ(group2) patients. Higher levels of the
inflammation marker CRP were associated with low
HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule
lipopolysaccharide reduced
HLA-DQ expression.
Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of
HLA-DQ expression in CF, which is associated with
inflammation and a reduced response to IFNγ.
KEY MESSAGE: • CF patients show a reduced expression of MHCII molecules in monocytes and macrophages. •
HLA-DQ and
HLA-DR transcript levels are also reduced in CF patients. • CF patient
C-reactive protein levels correlate with low
HLA-DQ expression. • Reduced expression of
MHC class II molecules appears to be linked to
inflammation. • CF patients exhibit an impaired response to IFNgamma.