Enhanced Complement Sensitivity of NK-T Cells in Murine Thymus and Spleen Associated with Presence of Serum Immunoglobulin

Onoé, Kazunori; Iwabuchi, Kazuya; Iwabuchi, Chikako; Tone, Saori; Konishi, Jun; Kawakami, Yoshihiro; Nishimura, Masaharu

doi:10.1078/0171-2985-00188

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…A decrease in circulating V α 24 + NKT cell numbers has also been reported in RA, SSc and a wide variety of autoimmune diseases [23,25,27]. These observations support the idea that NKT cells may function as regulatory T cells and that their quantitative and/or functional defects are associated either directly or indirectly with the development of these autoimmune diseases [36,37].…”

Section: Discussionsupporting

confidence: 60%

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

Takagi

Iwabuchi

et al. 2004

Clinical and Experimental Immunology

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SUMMARY The frequency of either CD4–8– (double negative; DN) or CD4+ Vα24+Vβ11+ NKT cells, the expression of CD1d and the binding of CD1d‐tetramer loaded with α‐galactosylceramide (α‐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+ Vα24+Vβ11+ NKT cells as well as CD1d‐α‐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 α‐GalCer. The dysfunction of NKT cells to recognize ligands such as α‐GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

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Section: Discussionsupporting

confidence: 60%

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

Takagi

Iwabuchi

et al. 2004

Clinical and Experimental Immunology

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“…Various abnormalities in the number and function of NKT cells have been observed in human autoimmune diseases (15,22,32,33) as well as in a variety of mouse strains that are genetically predisposed to the development of autoimmune diseases (34)(35)(36)(37)(38)(39). However, the regulatory role of NKT cells in the development of autoimmune arthritis has not been completely explored.…”

Section: Discussionmentioning

confidence: 99%

Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice

Takagi

Iwabuchi²,

Maeda³

et al. 2006

Int J Mol Med

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Abstract. Macrophage migration inhibitory factor (MIF)plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-IIC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIF Tg ) and wild-type C57BL/6 (WT) mice. We found that MIF Tg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIF Tg mice and significantly increased numbers of CD69 + T cells were detected in the spleens of these arthritic MIF Tg mice, compared with WT mice. Natural killer T (NKT) cells from MIF Tg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with ·-galactosylceramide (·-GalCer). Further, repeated administration of ·-GalCer to MIF Tg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play an ameliorating role upon stimulation with ·-GalCer in the inflammatory process in MIF Tg mice.

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The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement

Racila

Ritchie

et al. 2006

Immunogenetics

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Complement is one of primary defense mechanisms against intravascular microorganisms and could play a role in the immune response to malignancy and hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA associates with outcome in patients with breast carcinoma. Genotyping for C1qA[276A/G] was performed in 63 breast cancer subjects with localized tumor and compared with that in 38 breast cancer subjects with metastasis. Established risk factors for clinical outcome were considered and evaluated in multivariable analysis. Breast cancer subjects with heterozygous or homozygous C1qA[276G] genotype had a higher rate of metastasis than subjects with the homozygous C1qA[276A] genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1-4.1]. This association was stronger when only metastatic sites associated with hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR 3.5, 95% CI 1.4-5.6) and remained statistically significant after adjustment for the number of positive lymph nodes, estrogen receptor status, and progesterone receptor status. There was no statistical difference in the C1qA[276A/G] allelic distribution between all subjects with breast cancer and controls. These results suggest there could be an association of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites linked to hematogenous spread of disease. The C1qA polymorphism associated with decreased distant metastasis has also been correlated with an increased incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an altered immune response may play a role in the observed association.

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Enhanced Complement Sensitivity of NK-T Cells in Murine Thymus and Spleen Associated with Presence of Serum Immunoglobulin

Cited by 4 publications

References 41 publications

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

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

Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice

The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement

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