Wasp venom immunotherapy induces activation and homing of CD4+CD25+ forkhead box protein 3-positive regulatory T cells controlling TH1 responses

• Published in: Journal of allergy and clinical immunology 2011-02, Vol.127 (2), p.495-501
• Main Authors: KERSTAN, Andreas, ALBERT, Christa, KLEIN, Detlef, BRÖCKER, Eva-B, TRAUTMANN, Axel
• Format: Article
• Language: English
• Subjects: Age; Allergies; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Immunotherapy; Lymphocytes; Medical sciences; Methods; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Ultrasonic imaging; Venom
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.11.025

Background Despite a growing interest in CD4+CD25+forkhead box protein 3 (Foxp3)-positive regulatory T (Treg) cells, the fundamental parameters of the activation and homing of these cells during wasp venom immunotherapy (VIT) are largely unknown. Objective We investigated longitudinally the phenotype and function of Treg cells in a well-characterized homogeneous group of patients with wasp venom allergy during VIT. Methods In 30 patients peripheral Treg cells wereex vivomonitored for their activation status and homing capacities by means of flow cytometric analysis before and after 1 and 6 months of VIT. In addition, thein vitrosuppressive activity of Treg cells, as well as cytokine secretion, in response to wasp venom was analyzed. Results One month after initiating VIT, the proportion of both CD4+CD25+Foxp3+and CD4+Foxp3+Treg cells significantly decreased in peripheral blood. Coexpression of the lymph node homing receptors CCR7/CD62L were induced in CD4+Foxp3+CD45RO+Treg cells, indicating recirculation of VIT-activated Treg cells in secondary lymphoid organs.In vivoimaging by means of color duplex ultrasonography of the axillary draining lymph nodes demonstrated a VIT-induced 4-fold augmentation in afferent arterial blood flow. Furthermore, increased activation markers (CD45RO and HLA-DR) of Treg cells correlated with effectivein vitrosuppression of wasp venom-driven T-cell proliferation. After 1 month of VIT, Treg cell depletionin vitrogreatly enhanced wasp venom-induced IFN-γ secretion. Conclusions Allergen exposure during VIT simultaneously induces the activation and selective homing of circulating Treg cells. Functionally, on the one hand, Treg cells balance the immune reaction toward tolerance, and on the other hand, they are involved in controlling overwhelming TH1 responses.