Immunoregulatory defects of V alpha 24 super(+) V beta 11 super(+) NKT cells in development of Wegener's granulomatosis and relapsing polychondritis

• Published in: Clinical and experimental immunology 2004-06, Vol.136 (3), p.591-600
• Main Authors: Takagi, D, Iwabuchi, K, Iwabuchi, C, Nakamaru, Y, Maguchi, S, Ohwatari, R, Furuta, Y, Fukuda, S, Joyce, S, Onoe, K
• Format: Article
• Language: English
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2004.02471.x

The frequency of either CD4 super(-)8 super(-) (double negative; DN) or CD4 super(+) V alpha 24 super(+)V beta 11 super(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha -galactosylceramide ( alpha -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 super(+) V alpha 24 super(+)V beta 11 super(+) NKT cells as well as CD1d- alpha -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 super(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4 super(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4 super(+) 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 alpha -GalCer. The dysfunction of NKT cells to recognize ligands such as alpha -GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.