Impact of Sublingual and Oral Immunotherapy for Peanut Allergy on Blood Dendritic Cells

Dendritic cells (DCs) are key antigen presenting cells that direct tolerogenic and effector T cell functions. We evaluated how peanut sublingual (SLIT) and oral (OIT) immunotherapy altered DC responses. Blood was obtained from subjects at baseline and at multiple timepoints during a placebo-controlled trial comparing peanut OIT to SLIT. Plasmacytoid (pDC) and myeloid (mDC) were purified and cultured with autologous CD4+T cells. Allergen-induced cytokine secretion was measured in co-cultures by multiplexing technology, and expression of MHC II and costimulatory molecules on DCs by flow cytometry. Peanut-induced secretion of TH2 cytokines decreased in pDC-T and mDC-T co-cultures after 12 months of maintenance dosing with both OIT and SLIT (p<0.05). Levels of CD40, HLA-DR, and CD86 also decreased on DCs, while expression of CD80 increased (p<0.05). Effects were most striking in mDC-T cell co-cultures from subjects receiving OIT. These markers of immunologic suppression often reversed within weeks following withdrawal from IT, in some cases during ongoing maintenance therapy. Peanut-induced release of other effector cytokines, including IFN-g and IL-10, changed similarly to TH2 cytokines. Changes in DC-T cell responses did not correlate with clinical outcomes. Stimulation of co-cultures with dust mite led to cytokine changes that mimicked those seen with peanut. OIT and SLIT for peanut allergy induced marked suppression of dendritic cell activation and Th2 cytokine responses during the initial phases of IT in an antigen non-specific manner. While there was substantial inter-individual variation, in many subjects suppression appeared to be transient, even while on maintenance dosing.