Abnormal expression of chemokine receptors in Behçet's disease: relationship to intracellular Th1/Th2 cytokines and to clinical manifestations

Abstract

Dynamic interplay between cytokines and chemokines directs trafficking of peripheral blood mononuclear cells to tissues in autoimmune and/or viral diseases. The aim of the current study was to define the expression on CD3+ T cells of six chemokine receptors associated with inflammatory sites and the expression of intracellular cytokines, such as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), in Behcet's disease (BD). Flow cytometry was used to detect chemokine receptor and intracytoplasmic cytokines' expression. We observed that CD3+ T cells in the peripheral blood express a restricted array of inflammatory chemokine receptors, specifically, CCR5, CCR6 and CXCR3, but little CCR1-3. The highest expression of CXCR3 on CD3+ T cells is associated with the presence of central nervous system (CNS) manifestations or pulmonary involvement. CXCR3 is the principal inflammatory chemokine receptor involved in BD. CCR5 chemokine receptor is increased in BD regardless of clinical manifestations. The frequency of IFN-gamma-producing cells expressing CXCR3+ CD3+ cells is significantly increased in patients with BD compared with normal controls. IL-4-producing cells are decreased in BD. These results demonstrate the predominance of type 1 cytokine producing cells in CXCR3+ CD3+ T cells during BD. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in BD, particularly during CNS and pulmonary manifestations.