<b>Cytotoxic activity against tumour cells mediated by intermediate TCR cells in the liver and spleen</b>

Kawamura, Toshihiko; Kawachi, Yasuyuki; Moroda, Tetsuya; Weerasinghe, Anura; Iiai, Tsuneo; Seki, Shu; Tazawa, Yusaku; Takada, G.; Abo, Toru

doi:10.1046/j.1365-2567.1996.d01-719.x

Cited by 45 publications

(40 citation statements)

References 34 publications

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“…6). Primarily, lymphocytes isolated from the liver had high NK cytotoxicity but those isolated from the spleen and small intestine had low NK cytotoxicity (9). This tendency was confirmed in mice fed with or without β-glucan (Fig.…”

Section: Augmented Cytotoxicity Of Iel In the Small Intestine By β-Glmentioning

confidence: 54%

Potentiation of intestinal immunity by micellary mushroom extracts

et al. 2007

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Mushroom (shiitake) extracts were dispersed with lecithin micelles to prepare superfine particles (0.05 to 0.2 μm in diameter) of β-1,3-glucan (micellary mushroom extracts). When mice were fed with these micelles of β-glucan (0.75 mg/day/mouse, smaller amounts of β-glucan), the number of lymphocytes yielded by the small intestine increased by up to 40%. More interestingly, the ratio of CD8αβ + TCRαβ + cells/CD8αα + TCRαβ + cells increased prominently. In parallel with this deviation in the distribution of lymphocyte subsets, tumor cytotoxicity against P815 cells and cytokine productions were also augmented. In other words, phylogenetically developed lymphocytes (CD8αβ + , TCRαβ + ) were much more effectively activated by the oral administration of micellary β-glucan. These results suggest that smaller amounts of micellary β-glucan might be useful for the potentiation of intestinal immunity.It is empirically known that mushrooms, especially components of β-glucan, are good for our health (2,6,10,14,17,21) and sometimes show anti-tumor effects in animal models and humans (3,4,15). However, such anti-tumor effects of crude mushroom extracts were limited in our preliminary experiments. To overcome this, we prepared superfine particles of β-1,3-glucan (i.e., mushroom extracts) dispersed with lecithin micelles using a high-pressure emulsifier in this study. These mushroom (shiitake) extracts were then used to examine whether oral administration has the potential to induce the augmentation of intestinal immunity in mice. Cumulative evidence has revealed that the augmentation of intestinal immunity is extremely important for immunological tolerance, anti-tumor effects, innate immunity against intracellular pathogens, etc. (1,7,8,13,18). The present results indicate that micellary mushroom extracts might have such potential via the augmentation of intestinal immunity, especially in the small intestine. MATERIALS AND METHODSMice. C57BL/6 (B6) mice at the age of 8-10 weeks were used in this study. The mice were maintained in the animal facility of Niigata University (Niigata, Japan). All mice were fed under specific pathogenfree conditions. All experimental procedures were approved by the Committee on Animal Research of Niigata University.Oral administration of shiitake extracts. Shiitake mushrooms were broken down with a colloid mill and boiled at 95°C for 3 h in hot water, and the resulting extracts were filtered. These extracts were then mixed with lecithin and dispersed at 1500 kgf/ cm 2 with a high-pressure emulsifier (Ajinomoto Co. Inc., Kawasaki, Japan). Particles of β-1,3-glucan in the shiitake extracts (10~1000 μm) became smaller up to particle size of 0.05 to 0.2 μm (Fig. 1). The major component of the superfine particles was

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Section: Augmented Cytotoxicity Of Iel In the Small Intestine By β-Glmentioning

confidence: 54%

Potentiation of intestinal immunity by micellary mushroom extracts

et al. 2007

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“…We previously showed the distinct functional properties of extrathymic T cells and thymus-derived T cells. Namely, extrathymic T cells (TCR int cells) eliminate abnormal self-cells (mainly self-antigens in the context of monomorphic major histocompatibility complex antigen) because of their autoreactivity (i.e., innate immunity), [21][22][23][24] whereas thymus-derived T cells (TCR high cells) interact with foreign antigens (mainly in the FIG. 7.…”

Section: Discussionmentioning

confidence: 99%

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

et al. 1999

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We previously reported that extrathymic T cells (intermediate T-cell receptor cells [TCRIn a series of recent studies, 1-4 we have shown that the adult liver is one of the hematopoietic organs in mice, mainly producing extrathymic T cells (i.e., interleukin-2 receptor ␤ chain (IL-2R␤) ϩ intermediate T-cell receptor cells [TCR int cells]) and granulocytes from their own pre-existing precursor cells (i.e., c-kit ϩ Lin Ϫ stem cells). On the other hand, the bone marrow produces all hematopoietic cells, whereas the intestine (i.e., its cryptopatches) produces only extrathymic T cells. 5,6 Reflecting the above-mentioned situation, we have often encountered clusters of lymphoid and myeloid cells in the parenchymal space of the liver in normal or estrogentreated mice. 3 Because such clusters always contain c-kit ϩ Lin Ϫ cells and dividing cells (bromodeoxyuridine ϩ cells), 3,7 it is presumed that these clusters might be sites for the generation of extrathymic T cells and granulocytes in the liver. A similar phenomenon (i.e., c-kit ϩ Lin Ϫ cells giving rise to extrathymic T cells) occurs in the cryptopatches of the small intestine. 5,6 In the course of these studies, we observed that some lymphocytes also exist dispersely in the parenchymal space of the liver (including Glisson' s area) without cluster formation, even in normal adult mice. To determine the origin of these lymphocytes (namely, their being of extrathymic origin or of thymic origin), we intensively characterized the phenotype of cells before and after liver irrigation. Although intensive liver irrigation with physiological saline from the portal vein enriched extrathymic T cells (i.e., TCR int cells), thymus-

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“…Sympathetic nerve activation, possibly for the supply of oxygen and nutrients to proliferating hepatocytes, is always accompanied by hepatocyte regeneration. Because IL-2R␤ ϩ CD3 int cells can mediate self-reactive cytotoxicity, [21][22][23] it was also investigated how their cytotoxicity was modulated during hepatocyte regeneration. The biological significance of these cells at the time of hepatocyte regeneration is herein discussed in light of our findings.…”

mentioning

confidence: 99%

“…Cytotoxicity for YAC-1, EL-4, and thymocytes was examined by a 51 Cr-specific release assay with an incubation time of 4 hours, as previously described. 21 YAC-1 cells were an NK-sensitive target and EL-4 cells were an NK-resistant target (used as a negative control). Syngeneic thymocytes were used to determine self-reactive cytotoxicity mediated by CD3 int cells.…”

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confidence: 99%

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation

et al. 2000

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When C57BL/6 mice were partially hepatectomized (PHx), severe lymphocytosis was induced in the liver in the early phase of hepatocyte regeneration (4 to 12 hours after PHx). A major lymphocyte subset expanding in this organ was estimated to be natural killer 1.1 ؉ (NK1.1 ؉ ) intermediate CD3 (CD3 int ) cells (i.e., NKT cells). CD3 int cells are extrathymic T cells generated in situ in the liver. These changes were suppressed when mice with PHx were pretreated with a ␤ ␤-adrenergicD antagonist (i.e., ␤ ␤-blocker), propranolol (PPL). This might have been caused by sympathetic nerve stimulation during hepatocyte regeneration. An ␣ ␣-blocker showed a similar effect, although the magnitude of suppression was lower than that of the ␤ ␤-blocker. We previously showed that NK and NKT cells express surface ␤ ␤-adrenergic receptors and are activated in number by sympathetic nerve stimulation. In the present study, NK cytotoxicity mediated by liver lymphocytes obtained from mice with PHx decreased, whereas NKT cytotoxicity against syngeneic thymocytes increased. Purified CD3 int cells were also found to be able to mediate NKT cytotoxicity against regenerating hepatocytes. These results suggest that sympathetic nerve stimulation after PHx results in subsequent activation of NKT cells and that these NKT cells might be associated with immunologic surveillance during hepatocyte regeneration. (HEPATOLOGY 2000;31:907-915.)In a series of recent studies, we showed that extrathymically generated T cells (i.e., extrathymic T cells) are present in the liver.

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Cytotoxic activity against tumour cells mediated by intermediate TCR cells in the liver and spleen

Cited by 45 publications

References 34 publications

Potentiation of intestinal immunity by micellary mushroom extracts

Potentiation of intestinal immunity by micellary mushroom extracts

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation

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