Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis

James L. Kreindler, Chad Steele, Nikki Nguyen, Yvonne R. Chan, Joseph M. Pilewski, John F. Alcorn, Yatin M. Vyas, Shean J. Aujla, Peter Finelli, Megan Blanchard, Steven F. Zeigler, Alison Logar, Elizabeth Hartigan, Marcia Kurs-Lasky, Howard Rockette, Anuradha Ray, Jay K. Kolls

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126 Scopus citations

Abstract

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%-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. 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-β-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-β. This in vitro treatment also resulted in increased Treg TGF-β 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.

Original languageEnglish (US)
Pages (from-to)3242-3254
Number of pages13
JournalJournal of Clinical Investigation
Volume120
Issue number9
DOIs
StatePublished - Sep 1 2010

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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