Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.
Author:
Knutsen AP, Hutchinson PS, Albers GM, Consolino J, Smick J, Kurup VP.
Date: 22 December 2003
Abstract:
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterizedby a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and ahyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients withoutABPA. We hypothesize that one reason for this response is increased sensitivity tointerleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86 andleading to a positive amplification mechanism that increases Th2 CD4+ T cellresponses. METHODS: Peripheral blood mononuclear cells (PBMC) were isolatedfrom seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls andstimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48 h.The number of CD23 molecules and percentages of CD23+ B cells were quantified byflow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) andantigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmiccytokine synthesis enumerated by cytokine staining using flow cytometry to measureTh2 and Th1 CD3+ T cells. RESULTS: The numbers of CD23 molecules on B-cellswere significantly elevated at time 0 in ABPA CF patients compared with both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in vitro, thenumbers and percentages of CD23 expression on B cells were significantly upregulatedin ABPA CF patients compared with non-ABPA CF patients and controls.The IL-13 stimulation up-regulated CD23 expression; however, there was nosignificant difference in ABPA CF patients compared with non-ABPA CF patientsand controls. The percentages of interferon (IFN)-gamma+ CD3+T cells followingPMA/IO stimulation were significantly decreased in both ABPA and non-ABPA CFpatients compared with controls. There were no significant differences of IL-4+ andIL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When
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