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.
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-gamma and IL-4 were analysed by flow cytometry. Allergen-specific T cell proliferation was assessed by 3H-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-gamma 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.


CONCLUSIONS
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.
Department of Pathology and Immunology, Monash University, Melbourne, Victoria, Australia.
L M
LM
Gardner
F C
FC
Thien
J A
JA
Douglass
J M
JM
Rolland
R E
RE
O'Hehir
D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002465:Cell Movement; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D039441:Integrin alpha4 / Q000032:analysis; D016753:Interleukin-10 / Q000276:immunology*; D019041:L-Selectin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D015415:Biomarkers; D019713:Receptors, CCR5; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D016753:Interleukin-10; D039441:Integrin alpha4