Treatment with anti-OX40L or anti-TSLP does not alter the frequency of T regulatory cells in allergic asthmatics.

OX40-OX40L interactions and thymic stromal lymphopoietin (TSLP) are important in the induction and maintenance of Th2 responses in allergic disease, whereas T regulatory cells (Treg) have been shown to suppress pro-inflammatory Th2 responses. Both OX40L and TSLP have been implicated in the negative regulation of Treg. The effect of anti-asthma therapies on Treg is not well known. Our aim was to assess the effects of two monoclonal antibody therapies (anti-OX40L and anti-TSLP) on Treg frequency using a human model of allergic asthma. We hypothesized that the anti-inflammatory effects of these therapies would result in an increase in circulating Treg (CD4(+) CD25(+) CD127(low) Foxp3(+) cells) frequency. We measured Treg using flow cytometry, and our results showed that neither allergen challenge nor monoclonal antibody therapy altered circulating Treg frequency. These data highlight the need for assessment of airway Treg and for a more complete understanding of Treg biology so as to develop pharmacologics/biologics that modulate Treg for asthma therapy.

Hemopoietic progenitor cells and hemopoietic factors: potential targets for treatment of allergic inflammatory diseases.

Eosinophilic infiltration is a cardinal feature of allergic inflammation; based upon its biological actions, the eosinophil has assumed the role as the principal inflammatory cell in asthma. In assessing the mechanisms by which eosinophils are recruited to sites of inflammation, a sizeable body of evidence exists supporting the proposal that expansion of hemopoietic compartments in the bone marrow stimulates an increased turnover and traffic of mature eosinophils to the site of allergic inflammation. In addition, recent findings point to the possible egress and traffic of primitive progenitor cells to the site of inflammation where in-situ differentiation may provide a continued supply of pro-inflammatory cells. In the present article, we will review the evidence for these findings, and discuss the rationale for targeting hemopoiesis and migrational pathways of hemopoietic cells in the treatment of allergic disease. In this context, we will discuss the effect of corticosteroid treatment on hemopoietic mechanisms; the effects of therapies that inhibit the actions of cysteinyl leukotrienes (CysLTs); the effects of in vivo blockade of the eosinophil-active cytokine, interleukin (IL)-5; and, the effects of antihistamines on hemopoiesis. In addition, we will address the potential role that small molecular weight chemokine receptor antagonists may play in modulating progenitor cell trafficking to tissue sites of inflammation.