A defect of CD4+CD25+ regulatory T cells in inducing interleukin-10 production from CD4+ T cells under CD46 costimulation in asthma patients.
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.
Xu
Ya-Qing
YQ
Department of Respiratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
Gao
Ya-Dong
YD
Yang
Jiong
J
Guo
Wei
W
D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D051916:Membrane Cofactor Protein / Q000378:metabolism / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D018106:CD28 Antigens; D005938:Glucocorticoids; D053645:Interleukin-2 Receptor alpha Subunit; D051916:Membrane Cofactor Protein; D016753:Interleukin-10