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 profil e of T(H)2 effectors could be reversed by exploiting their selective expres sion 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 pr ofile of cytokine production by TH2 cells from allergic subjects was relate d 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 pr ofile, thus providing the physiologic basis for new immunotherapeutic strat egies in allergic disorders.