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1,25‐dihydroxyvitamin D 3 enhances the ability of transferred CD4 + CD25 + cells to modulate T helper type 2‐driven asthmatic responses
Author(s) -
Gorman Shelley,
Judge Melinda A.,
Burchell Jennifer T.,
Turner Debra J.,
Hart Prue H.
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03222.x
Subject(s) - il 2 receptor , biology , physics , microbiology and biotechnology , immunology , t cell , immune system
Summary The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], are yet to be fully elucidated. In this study, naturally occurring CD4 + CD25 + cells from the skin‐draining lymph nodes (SDLN) of mice treated with topical 1,25(OH) 2 D 3 had an increased ability to suppress T helper type 2 (Th2) ‐skewed immune responses. CD4 + CD25 + cells transferred from mice treated with topical 1,25(OH) 2 D 3 into ovalbumin (OVA) ‐sensitized mice challenged intranasally with OVA 18 hr later, significantly suppressed the capacity of airway‐draining lymph node (ADLN) cells to proliferate and secrete cytokines in response to further OVA stimulation ex vivo . The CD4 + CD25 + cells from 1,25(OH) 2 D 3 ‐treated mice also reduced airway hyperresponsiveness and the proportions of neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF). To test the effect of 1,25(OH) 2 D 3 on cells able to respond to a specific antigen, CD4 + CD25 + cells were purified from the SDLN of OVA‐T‐cell receptor (TCR) transgenic mice treated 4 days earlier with topical 1,25(OH) 2 D 3 . CD4 + CD25 + cells from OVA‐TCR mice treated with 1,25(OH) 2 D 3 were able to alter BALF cell content and suppress ADLN responses to a similar degree to those cells from non‐transgenic mice, suggesting that the effect of 1,25(OH) 2 D 3 was not related to TCR signalling. In summary, topical 1,25(OH) 2 D 3 increased the regulatory capacity of CD4 + CD25 + cells from the SDLN to suppress Th2‐mediated allergic airway disease. This work highlights how local 1,25(OH) 2 D 3 production by lung epithelial cells may modulate the suppressive activity of local regulatory T cells.