Gamma Delta (γδ) T Cells and Their Involvement in Behçet's Disease

Abstract

Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role. γδ T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of γδ T cells in BD. We review the literature and discuss the roles that γδ T cells may play in BD pathogenesis.

Figure 1

Schematic diagram of the potential interaction of neutrophils, monocytes, and DCs with γδ T cells in BD. An infectious trigger (e.g., microbes) results in extravasation of neutrophils and following phagocytosis of the invading microbes, neutrophils release traces of HMB-PP into the microenvironment where γδ T cells sense it. Monocytes then might take up or bind this soluble HMB-PP and present it to γδ T cells. This interaction triggers TNFα secretion, a proinflammatory cytokine along with other similar cytokines including IFNγ which promotes γδ T cell expansion and drive local chemokine (CXCL8) production that further recruits new neutrophils and monocytes to the site of infection. In addition, activated γδ T cells keep providing survival and activation signals to the newly recruited neutrophils and monocytes by secreting TNFα. Furthermore, activated γδ T cells present antigen to DCs and thus initiate Th1, Th2, and Th17 differentiation and proliferation. Even if the infectious trigger is in the form of a non-HMB-PP source such as HSP60/65, γδ T cells can again respond by expanding and keep the interaction active with the neighbouring cells.