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Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus.
It occurs in 4% to 15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA.
Therefore, we compared cohorts of A. fumigatus-colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization.
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We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A. fumigatus in peripheral CD4+ T cells isolated from patients with ABPA. In contrast, CD4+ T cells from the non-ABPA cohort did not mount enhanced Th2 responses in vitro and contained a higher frequency of TGF-beta–expressing regulatory T cells.
Heightened Th2 reactivity in the ABPA cohort correlated with lower mean serum vitamin D levels. Further, in vitro addition of 1,25 OH-vitamin D3 substantially reduced DC expression of OX40L and increased DC expression of TGF-beta.
This in vitro treatment also resulted in increased Treg TGF-beta expression and reduced Th2 responses by CD4+ T cells from patients with ABPA.
These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF.
Source: The Journal of Clinical Investigation, Aug 16, 2010, PMID: 20714107, by Kreindler JL, Steele C, Nguyen N, Chan YR, Pilewski JM, Alcorn JF, Vyas YM, Aujla SJ, Finelli P, Blanchard M, Zeigler SF, Logar A, Hartigan E, Kurs-Lasky M, Rockette H, Ray A, Kolls JK. Children’s Hospital of Pittsburgh; Graduate School of Public Health and Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pennsylvania; University of Alabama at Birmingham; Louisiana State University Health Sciences Center, New Orleans; Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA. [Email: