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Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4 + CD25 + interleukin‐10 + T cells expressing peripheral tissue trafficking markers
Author(s) -
Gardner L. M.,
Thien F. C.,
Douglass J. A.,
Rolland J. M.,
O'Hehir R. E.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.02009.x
Subject(s) - immunology , cd8 , il 2 receptor , medicine , cytokine , immunotherapy , house dust mite , t cell , aldesleukin , interleukin 2 , immune system , allergy , allergen
Summary Background Clinically effective subcutaneous allergen‐specific immunotherapy (SIT) is associated with altered circulating T cell cytokine production and altered local cytokine responses with increased IL‐10 following allergen challenge in target organs. Objective This study aimed to elucidate mechanisms for these T cell changes, by examining surface expression of markers for peripheral tissue trafficking on circulating cytokine‐positive T cells following standardized house dust mite‐ (HDM‐) SIT. Methods A randomized conventional HDM immunotherapy study was performed on a panel of 12 HDM‐allergic subjects. Nine subjects received treatment with conventional HDM immunotherapy using a standardized extract and three subjects were treated by standard pharmacotherapy alone. Symptom and medication scores and allergen‐induced cutaneous late‐phase responses were assessed before and 9 months after institution of therapy. Before and at 3 and 9 months of SIT, peripheral blood mononuclear cells were cultured for 14 days with HDM extract and CD4 + and CD8 + T cell expression of CD62L, CD49d and CCR5 and production of IL‐10, IFN‐γ and IL‐4 were analysed by flow cytometry. Allergen‐specific T cell proliferation was assessed by 3 H‐thymidine incorporation. Results At 9 months, all SIT‐treated patients showed reduced symptom scores and late‐phase cutaneous responses to HDM compared with baseline levels. The proportions of CD4 + T cells which were IL‐10 + were increased ( P <0.01), and the proportions of CD4 + and CD8 + T cells which were IL‐4 + decreased ( P <0.05) compared with baseline. CD4 + and CD8 + T cell IFN‐γ production, expression of surface markers for peripheral tissue trafficking and allergen‐specific proliferation remained unchanged during SIT treatment. However, increased proportions of CD4 + CD62L − , CD4 + CD49d hi , CD4 + CCR5 + T cells expressing IL‐10 were detected at 9 months of SIT compared with baseline ( P <0.05). IL‐10 staining co‐localized with CD4 + CD25 + T cells. Conclusion Clinically effective subcutaneous immunotherapy with a standardized HDM Dermatophagoides pteronyssinus preparation results in decreased numbers of IL‐4 + T cells and expansion of CD4 + IL‐10 + T cells expressing a peripheral tissue trafficking phenotype. The co‐localization of IL‐10 + staining to CD4 + CD25 + T cells is consistent with the induction of a T regulatory cell population by SIT.