Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behçet's disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity

Abstract

Introduction: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vgamma9/Vdelta2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity.

Methods: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vgamma9/Vdelta2 T lymphocytes by means of fluorescence-activated cell sorter analysis of lymphocyte cultures from patients with active and inactive BD and healthy subjects.

Results: Cell expansion, expression of TNFRII, perforin and gamma IFN content and release of granzyme A were significantly higher in active patients. In vitro and ex vivo treatment with infliximab resulted in a significant reduction of all parameters together with changes in the phenotype of Vgamma9/Vdelta2 T cells.

Conclusions: All together these data indicate that infliximab is capable of interfering with Vgamma9/Vdelta2 T cell function in BD and although cell culture models cannot reliably predict all potential effects of the drug in vivo, our results present the possibility that this drug may find use in a range of immunological disorders, characterized by dysregulated cell-mediated immunity.

Figure 1

Effects of in vitro addition of Infliximab (10, 50 and 100 μg/ml) to the cultures from active patients. (a) Expansion of Vγ9Vδ2 T lymphocytes (%); (b) TNF-RII (MESF); (c) IFN-γ content (%) and (d) granzyme release (mOD).

Figure 2

Percentage of Vγ9/Vδ2 cells isolated from active patients cultured in presence of Infliximab (50 μg/ml). (a) Effector CD45RO⁺CD27^-; (b) Cytotoxic CD45RO^-CD27^-; (c) Memory CD45RO⁺CD27⁺; naive CD45RO^-CD27⁺.