Reversal of human allergen-specific CRTH2+ T(H)2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide.
BACKGROUND
The chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) is a receptor for prostaglandin D(2), which among human T cells is selectively expressed by T(H)2 and type 2 cytotoxic effectors.


OBJECTIVE
Our purpose was to assess whether the cytokine production profile of T(H)2 effectors could be reversed by exploiting their selective expression of CRTH2.


METHODS
CRTH2(+) T cells were purified from the blood of allergic subjects, stimulated with the specific allergen in the absence or presence of IL-12, and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma after antigen or polyclonal stimulation.


RESULTS
Both IL-12 and the PS-DSP30 oligodeoxynucleotide enabled CRTH2(+) allergen-stimulated T(H)2 cells to produce IFN-gamma. This change in the profile of cytokine production by T(H)2 cells from allergic subjects was related to the upregulation of IL-12 receptor beta2 chain and was associated with the loss of CRTH2.


CONCLUSIONS
These data demonstrate that the cytokine production pattern of fully differentiated T(H)2 effectors can be changed to a less polarized profile, thus providing the physiologic basis for new immunotherapeutic strategies in allergic disorders.
Annunziato
F
F
Department of Internal Medicine, Section of Clinical Immunology, Allergy and Respiratory Diseases, University of Florence, Italy.
Cosmi
L
L
Manetti
R
R
Brugnolo
F
F
Parronchi
P
P
Maggi
E
E
Nagata
K
K
Romagnani
S
S
D000485:Allergens / Q000276:immunology; D039741:Antigens, Dermatophagoides; D002460:Cell Line; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D011982:Receptors, Prostaglandin; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; C508439:IL12RB2 protein, human; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011982:Receptors, Prostaglandin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; C036293:prostaglandin D2 receptor