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

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) 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 wit...

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Bibliographic Details
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, Onoé, K
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antigens, CD1 - immunology
Ceramides - pharmacology
Female
Flow Cytometry
Granulomatosis with Polyangiitis - immunology
Humans
Interferon-gamma - immunology
Interleukin-4 - immunology
Killer Cells, Natural - immunology
Lymphocyte Activation
Lymphocyte Count
Male
Middle Aged
Polychondritis, Relapsing - immunology
Receptors, Antigen, T-Cell, gamma-delta - immunology
Th1 Cells - immunology
Th2 Cells - immunology
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Summary:The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) 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(+) V alpha 24(+)V beta 11(+) 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(+) 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 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.
ISSN:0009-9104