A defect of CD4+CD25+ regulatory T cells in inducing interleukin-10 production from CD4+ T cells under CD46 costimulation in asthma patients

Abstract

Background: The suppressive cytokine interleukin-10 (IL-10) plays a central role in disease control and clinical therapies of asthma. CD46 was recently identified as costimulatory molecule in inducing IL-10-producing regulatory T cells type 1 (Tr1) from CD4(+) T cells. Alterations in CD46 costimulation pathway were shown to be associated with multiple sclerosis and hemodialysis. In this study, the authors investigated alterations in CD46 costimulatory pathway in asthma.

Methods: CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells were isolated from peripheral blood mononuclear cells (PBMCs) of asthma patients (n = 13) and healthy subjects (n = 17). Both subsets of CD4(+) T cells were cultured alone or cocultured at a ratio of 1:10 under stimulation with CD3/CD28 or CD3/CD46, and the production of IL-10 in the supernatants was assessed by enzyme-linked immunosorbent assay (ELISA), the proliferation rates of the cells were determined with thymidine incorporation assay.

Results: Levels of IL-10 in the supernatants were higher in undivided CD4(+) T cells and 1:10 cocultured CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T cells than in CD4(+)CD25(+) Tregs or CD4(+)CD25(-) T cells alone, either under CD46 or under CD28 costimulation, both in healthy controls (n = 9) and in asthma patients (n = 7). Under anti-CD3/CD46 stimulation, IL-10 production in undivided CD4(+) T cells and cocultured T cells from asthma patients was lower than that in healthy controls. When treated with glucocorticoids, IL-10 production in undivided CD4(+) T cells and 1:10 cocultured CD4(+) T cells was not different between asthma patients (n = 6) and healthy controls (n = 8). The proliferation rates and the surface expression of CD46 were not different in T cells from both groups.

Conclusions: This study identified a new functional defect of CD4(+)CD25(+) Tregs in inducing IL-10 production from CD4(+)CD25(-) T cells under CD46 costimulation in asthma patients, which may be involved in the pathogenesis of allergic asthma.