Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites.
BACKGROUND
Dendritic cells (DCs) regulate the immune response to allergens in the lung; they induce either effector or regulatory T cells, which promote or suppress, respectively, the development of allergy. IL-10 is a potent immunosuppressive cytokine that induces type 1 regulatory (Tr1) T cells.


OBJECTIVE
To generate allergen-specific Tr1 cells in vitro from children with allergy.


METHODS
Monocyte-derived DCs from children with allergy to house dust mites (HDM) were generated by incubating the cells with IL-10 and pulsing them with Der p 2, a major HDM allergen, or by pulsing them with Der p 2 and incubating them with IL-10 during their last 2 days of differentiation.


RESULTS
Der p 2-specific T-cell proliferation and T(H)2 cytokine production were significantly reduced when T cells from patients with allergy to HDM were activated with autologous Der p 2-pulsed DCs that had been differentiated or incubated with IL-10. T-cell lines generated with Der p 2-pulsed DCs that were differentiated with IL-10 were hyporesponsive to reactivation with Der p 2 and able to suppress Der p 2-specific T(H)2 effector cells.


CONCLUSIONS
Dendritic cells differentiated in the presence of IL-10 and pulsed with allergen gave rise to a population of tolerogenic DCs that induced allergen-specific Tr1 cells. This finding represents an important step forward to the prospective clinical application of tolerogenic DCs to modulate allergen-specific T-cell responses.
Department of Pediatric Medicine, Immuno-Infectivology Unit, Bambino Gesu' Children's Hospital, Rome, Italy.
Valentina
V
Pacciani
Silvia
S
Gregori
Loredana
L
Chini
Stefania
S
Corrente
Marco
M
Chianca
Viviana
V
Moschese
Paolo
P
Rossi
Maria Grazia
MG
Roncarolo
Federica
F
Angelini
D000293:Adolescent; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D017635:Clonal Anergy / Q000276:immunology; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D039981:Pyroglyphidae / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D016753:Interleukin-10; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1