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

Abstract CD8-positive γδ T lymphocytes (GDCD8 + ) are specifically increased in peripheral blood of Behcet’s disease (BD) patients. GDCD8 + have shown a T regulatory (T reg ) function in autoimmune experimental models, human tumor infiltrates and intestinal intraepithelial lymphocytes from celiac patients. The aim of this study was to evaluate the T reg function of GDCD8 + and GDCD8 − , freshly isolated from peripheral blood, in comparison to CD4 + CD25 high naturally occurring T reg cells (nT reg ) in BD and healthy controls (HC). We tested their suppressive activity on CD4 + CD25 − T effector cells (T eff ) 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 T eff 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 nT regs. In conclusion, peripheral GD could contribute more to the dysregulation of TH1 type of cytokines than to exerting a T reg function in BD.