In vitro evaluation of γδ T cells regulatory function in Behçet’s disease patients and healthy controls

CD8-positive γδ T lymphocytes (GDCD8+) are specifically increased in peripheral blood of Behçet’s disease (BD) patients. GDCD8+ have shown a T regulatory (Treg) function in autoimmune experimental models, human tumor infiltrates and intestinal intraepithelial lymphocytes from celiac patients. The aim of this study was to evaluate the Treg function of GDCD8+ and GDCD8−, freshly isolated from peripheral blood, in comparison to CD4+CD25high naturally occurring Treg cells (nTreg) in BD and healthy controls (HC).We tested their suppressive activity on CD4+CD25− T effector cells (Teff) proliferation by a CFSE dilution protocol, after suboptimal activation with anti-CD3, in the absence or presence of IL-2. Furthermore, secreted cytokines and suppressive latency associated peptide (LAP)-TGFβ surface upregulation were determined after GD activation.We found that Vδ1 chains contribution to GDCD8+ was higher in BD than in HC, but neither GDCD8+ nor GDCD8−; (i) suppressed Teff proliferation, (ii) expressed LAP-TGFβ (iii) nor secreted IL-10, in either group. Moreover, GD presented a proinflammatory cytokine profile, mainly producing IFNγ and TNFα, in contrast to nTregs.In conclusion, peripheral GD could contribute more to the dysregulation of TH1 type of cytokines than to exerting a Treg function in BD.