Immunoregulatory defects of Vα24+Vβ11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis

SUMMARY The frequency of either CD4 ‐ 8 ‐ (double negative; DN) or CD4 + V a 24 + V b 11 + NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with a -galactosylceramide ( a -GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener’s granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4 + V a 24 + V b 11 + NKT cells as well as CD1d- a -GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4 + T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4 + NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4 + NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to a -GalCer. The dysfunction of NKT cells to recognize ligands such as a GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.