Mouse liver T cells: Their change with aging and in comparison with peripheral T cells

Tsukahara, Akihiro; Seki, Shu; Iiai, Tsuneo; Moroda, Tetsuya; Watanabe, Hirotaka; Suzuki, Susumu; Tada, Takashi; Hiraide, Hoshio; Hatakeyama, Katsuyoshi; Abo, Toru

doi:10.1002/hep.510260208

Cited by 125 publications

(126 citation statements)

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“…Together with our recent findings [37,42], it is noteworthy that two types of unconventional T cells with intermediate TCR [43], namely both NKT cells and CD8 + CD122 + T cells, can be directly or indirectly involved in either anti-tumor immunity or multi-organ failure. …”

Section: Cd8supporting

confidence: 82%

“…We also recently reported that not only NKT cells and NK cells but also CD8 + CD122 + T cells are essential anti-tumor effectors in mice injected with a-galactosylceramide [42]. These cells thereby could be involved in the immunological changes with aging, particularly regarding the anti-infection or antitumor immunity [25,43,44]. Interestingly, the liver CD8 + CD122 + T cells that increase in number with age have a capacity to produce a large amount of IFN-c by the IL-12 stimulation, as demonstrated in the present study.…”

Section: Discussionmentioning

confidence: 97%

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Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

et al. 2005

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We examined the role of mouse CD8+ CD122+ T cells, which increase in number with age, in the generalized Shwartzman reaction. This reaction was induced by IL‐12 priming and subsequent LPS challenge (after 24 h) in mice of various ages (4–50 weeks of age). Although most young mice (4 or 6 weeks of age) survived, mortality essentially increased with increasing age of the mice, and all mice of 20 weeks of age or older died within 48 h. Serum TNF‐α levels after LPS challenge also increased age dependently. The neutralization of either IL‐12‐induced IFN‐γ or LPS‐induced TNF‐α improved the survival of middle‐aged (25‐week‐old) mice. Both IFN‐γ production after IL‐12 priming and TNF‐α production from the liver mononuclear cells after LPS challenge were also prominent in the middle‐aged mice. CD8+CD122+ T cells cultured with IL‐12 produced a much larger amount of IFN‐γ than CD8+CD122– T cells. Although the depletion of NK/NK T cells did not decrease the IFN‐γ or TNF‐α production in the Shwartzman reaction of the middle‐aged mice, an additional depletion of CD8+CD122+ T cells did decrease such production and also improved mouse survival. Furthermore, young mice transferred with CD8+CD122+ T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.

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Section: Cd8supporting

confidence: 82%

Section: Discussionmentioning

confidence: 97%

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

et al. 2005

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“…Flow cytometry studies in mice have shown an age-related decrease in TCR ab T cells and concurrent increase in TCR gd T cells in the liver (Tsukahara et al 1997). Immunohistochemistry studies performed on the liver of aged mice revealed clusters or foci of immune cells, preferentially located near perivascular regions (Singh et al 2008 increased immune cell infiltration, with a shift from TCR ab to TCR gd T cells.…”

Section: Characteristics Of Hepatic Lymphoid Cell Populationsmentioning

confidence: 99%

Immune Functioning in Non lymphoid Organs: The Liver

Parker

Picut

2011

Toxicol Pathol

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The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are important in the nonspecific cell killing that is important in resistance to tumor cell invasion. The liver has a major role in deletion of activated T cells and induction of tolerance to ingested and self-antigens. Disposal of waste molecules generated through inflammatory, immunologic, or general homeostatic processes is accomplished via the action of specific endocytic receptors on sinusoidal endothelial cells of the liver. Age-related changes in sinusoids (pseudocapillarization), autophagy, and functions of various hepatic cell populations result in substantial alterations in many of these immunologically important functions.

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“…7,8 On the other hand, livers from mice and humans have recently been reported to contain not only a large population of NK cells but also of T cells with NK cell markers. [9][10][11][12][13] Namely, mouse NK1.1 antigen ϩ T (NKT) cells and human CD56 ϩ T cells are abundant in the livers. NKT cells in mice were activated by IL-12 and inhibited tumor metastases in the liver of mice 10,11,[14][15][16] (for a review, see Seki et al, 16 ).…”

mentioning

confidence: 99%

Decrease of Cd56+T Cells and Natural Killer Cells in Cirrhotic Livers With Hepatitis C May Be Involved in Their Susceptibility to Hepatocellular Carcinoma

et al. 2000

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Chronic viral hepatitis patients, especially hepatitis C patients, often fall victim to liver cirrhosis and subsequent hepatocellular carcinoma (HCC). 1 It is now believed that the HCV infection in hepatocytes itself is not cytopathic whereas the cellular immune response to infected hepatocytes may indeed cause hepatocyte injury. 1 It has been suggested that nonspecific NK cell activation 1,2 and viral antigen-specific activation of either CD4 ϩ T cells or cytotoxic CD8 ϩ T cells may be responsible for hepatocyte injury. 1,3-6 Consistent with this hypothesis, it has also been reported that liver lymphocytes expressed T helper 1 cytokine, IFN-␥, and IL-2 messenger RNA, and the serum levels of these cytokines were elevated in the patients with HCV. 7,8 On the other hand, livers from mice and humans have recently been reported to contain not only a large population of NK cells but also of T cells with NK cell markers. 9-13 Namely, mouse NK1.1 antigen ϩ T (NKT) cells and human CD56 ϩ T cells are abundant in the livers. NKT cells in mice were activated by IL-12 and inhibited tumor metastases in the liver of mice 10,11,14-16 (for a review, see Seki et al.,16 ). Human peripheral blood CD56 ϩ T cells were also activated in vitro by IL-12 and thus acquired an antitumor cytotoxicity against NK-resistant tumors. 13 Furthermore, strongly activated mouse liver NKT cells destroyed the syngeneic hepatocytes. 17 Therefore, the possibility has been raised that human CD56 ϩ T cells may also play an important role in both hepatocyte injury in chronic viral hepatitis and antitumor immunity in the liver. In the present study, we show that human liver MNC activated by anti-CD3 Ab or a combination of IL-2 and IL-12 (or IL-2 alone) both produced IFN-␥ and killed tumors more effectively than did PBMC. Furthermore, human liver CD56 ϩ T cells and CD56 ϩ NK cells gradually decreased in parallel with the progress of the hepatitis C and diminished in livers with cirrhosis. These liver MNC from cirrhotic livers could not effectively produce IFN-␥ and could not effectively kill not only K562 cells and Raji cells but also a human HCC cell line, HuH-7 cells, thus suggesting that the decrease in CD56 ϩ T cells and NK cells may be one of the mechanisms explaining why HCC frequently originates from cirrhotic livers. PATIENTS AND METHODSPatients and Liver Specimens. Liver specimens were obtained during surgery from the patients listed in Table 1 after obtaining their informed consent. Liver specimens obtained from the anti-HCV Aband HBs antigen (Ag)-negative patients with cancers other than HCC and were regarded as the HCV (Ϫ) liver specimens. Other liver specimens were from anti-HCV Ab-positive patients with chronic hepatitis C or with liver cirrhosis. Peripheral blood samples were also obtained during surgery. All liver specimens were obtained from areas other than tumor nodules.Reagents. Anti-CD3 Ab (UCHT1, mouse IgG1) were purchased from PharMingen (San Diego, CA). Recombinant human IL-2 and IL-12 were purchased from PEPRO TECH EC (London, UK). ...

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Mouse liver T cells: Their change with aging and in comparison with peripheral T cells

Cited by 125 publications

References 49 publications

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

Immune Functioning in Non lymphoid Organs: The Liver

Decrease of Cd56+T Cells and Natural Killer Cells in Cirrhotic Livers With Hepatitis C May Be Involved in Their Susceptibility to Hepatocellular Carcinoma

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Mouse liver T cells: Their change with aging and in comparison with peripheral T cells

Cited by 125 publications

References 49 publications

Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice

Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice

Immune Functioning in Non lymphoid Organs: The Liver

Decrease of Cd56+T Cells and Natural Killer Cells in Cirrhotic Livers With Hepatitis C May Be Involved in Their Susceptibility to Hepatocellular Carcinoma

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Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice