Abstract
People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months–53 years old) and 78 healthy controls (2–61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-β+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-β+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-β+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.
Highlights
T cell-mediated immune responses in people with cystic fibrosis (CF) have been reported to be biased towards either T helper (Th)2- or Th17-dominated responses [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
We evaluated the absolute numbers of these cells in those participants for whom differential counts were available: the CF group had low to normal absolute numbers of lymphocytes (0.4–4.5 × 109/L) and CD4+ cells (250–1500 cells/mL), and consideration of absolute numbers increased the variability but did not alter the relationships
A similar finding has been reported for people with chronic obstructive pulmonary disease (COPD), in that study, the overall Th17% was higher in COPD patients than in controls [24]
Summary
T cell-mediated immune responses in people with cystic fibrosis (CF) have been reported to be biased towards either T helper (Th)2- or Th17-dominated responses [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. The high prevalence of Th2-mediated allergic bronchopulmonary aspergillosis [15] and the presence of a high number of Th17 cells and cytokines in airways or lung-draining lymph nodes from people with CF [13] support this concept. Blood Th17 and Lung Function in Cystic Fibrosis and analysis, decision to publish, or preparation of the manuscript The extent to which these alterations are directly related to dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is not clear, PLOS ONE | DOI:10.1371/journal.pone.0120912 March 24, 2015
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