Journal article
Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis
The Journal of clinical investigation, Vol.120(9), pp.3242-3254
09/01/2010
DOI: 10.1172/JCI42388
PMCID: PMC2929900
PMID: 20714107
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 D
3
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.
Details
- Title: Subtitle
- Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis
- Creators
- James L Kreindler - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAChad Steele - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USANikki Nguyen - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAYvonne R Chan - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAJoseph M Pilewski - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAJohn F Alcorn - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAYatin M Vyas - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAShean J Aujla - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAPeter Finelli - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAMegan Blanchard - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USASteven F Zeigler - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAAlison Logar - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAElizabeth Hartigan - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAMarcia Kurs-Lasky - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAHoward Rockette - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAAnuradha Ray - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USAJay K Kolls - Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.120(9), pp.3242-3254
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI42388
- PMID
- 20714107
- PMCID
- PMC2929900
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 09/01/2010
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9984093457102771
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