Abstract
IntroductionBehcet's disease (BD) is a multi-systemic disorder with muco-cutaneous, ocular, arthritic, vascular or central nervous system involvement. The role of γδ T cells is implicated in BD. The activation status of γδ T cells and their cytokine secretion against phosphoantigens are evaluated in BD.MethodsNKG2A, NKG2C, NKG2D, CD16 and CCR7 molecules on γδ T cells were analyzed in 70 BD, 27 tuberculosis (TB) patients and 26 healthy controls (HC). Peripheral γδ T cells were expanded with a phosphoantigen (BrHPP) and IL-2, restimulated with BrHPP and a TLR3 ligand, and cytokine production was measured.Resultsγδ T cells were not increased in both BD and TB patients, but the proportions of TCRVδ2+ T cells were lower (58.9 and 50.7 vs. 71.7%, P = 0.04 and P = 0.005) compared to HC. Higher proportion of TCRVδ2+ T cells were CD16+ (26.2 and 33.9 vs. 16.6%, P = 0.02 and P = 0.001) and CCR7- (32.2 and 27.9 vs. 17.7%, P < 0.0001 and P = 0.014) in BD and TB patients compared to HC. NKG2C+ γδ+ T cells were relatively increased (0.5 and 0.6 vs. 0.3%, P = 0.008 and 0.018), whereas NKG2D positivity was decreased in patients with BD and TB (77.7 and 75.8 vs. 87.5%, P = 0.001 and 0.004). Expansion capacity of γδ T cells in BD and TB as well as production of IL-13, IFN-γ, granulocyte monocyte colony stimulating factor (GM-CSF), TNF-α, CCL4 and CCL5 in BD was lower compared to HC, when restimulated by TLR3 ligand and BrHPP.ConclusionThe changes on γδ T cells of BD as well as TB patients implicate that γδ T cells have already been exposed to regulatory effects, which changed their activity. Lower cytokine response of γδ T cells implicates down modulation of these cells in BD.
Highlights
Behcet’s disease (BD) is a multi-systemic disorder with muco-cutaneous, ocular, arthritic, vascular or central nervous system involvement
Phenotype of gδ T lymphocytes in peripheral blood The proportions of gδ+ T cells in peripheral blood mononuclear cells (PBMCs) were relatively low in BD patients and in both disease (TB) and healthy control (HC) groups (Table 2)
When compared among the pan gδ+ T cells, the dominance of TCRVδ2+ T cells was less prominent in BD and in the inactive BD (IA-BD) group compared to healthy controls (HC)
Summary
Behcet’s disease (BD) is a multi-systemic disorder with muco-cutaneous, ocular, arthritic, vascular or central nervous system involvement. The activation status of gδ T cells and their cytokine secretion against phosphoantigens are evaluated in BD. Behcet’s disease (BD) is a systemic inflammatory disorder with a diverse spectrum of clinical manifestations including mucocutaneous, ocular, vascular, gastro-intestinal, musculoskeletal and central nervous system involvements. A complex genetic background leading to a pro-inflammatory, innate immune system derived activation perpetuated by adaptive immune responses against environmental or auto-antigens is considered as the pathogenic mechanism in BD [1,2,3]. In adults with negative purified protein derivative (PPD) response, TCRVg9Vδ2+ T cells reacting to isopentenyl pyrophosphate (IPP) secrete Th1 type cytokines (IFN-g, TNF-a) and MIP-1b (CCL4) [5]. The expression of CD16 regulated cytolytic activity and production of inflammatory cytokines of the gδ T cells
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