The composition of intrahepatic lymphocytes: shaped by selective recruitment?

Klugewitz, Katja; Adams, David H.; Emoto, Masashi; Eulenburg, Katharina; Hamann, Alf

doi:10.1016/j.it.2004.09.006

Cited by 82 publications

(88 citation statements)

References 41 publications

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“…18 The liver also plays a key role in the innate immune response by influencing the homing and differentiation of NK cells. [31][32][33][34] Up to 65% of all lymphocytes present in the normal liver consists of NK cells, NKT cells, and cd T cells, and the frequency of NK cells among human intrahepatic lymphocytes ranges between 25% and 30%. 31,32 Furthermore, NK cells are located in the liver sinusoids, adherent to the liver sinusoidal endothelial cells and, thus, are well situated to eliminate arriving metastasizing tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Patient survival by Hsp70 membrane phenotype

Pfister

Radons

Busch

et al. 2007

Cancer

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BACKGROUNDHeat shock proteins (HSPs) play important roles in tumor immunity. The authors prospectively investigated the correlation between the tumor‐specific Hsp70 membrane expression as an independent clinicopathological marker and overall survival in tumor entities that differ in their route of metastasis.METHODSHsp70 membrane expression was examined by flow cytometry in 58 colon, 19 gastric, 54 lower rectal carcinoma, and 19 squamous cell carcinoma specimens and the corresponding normal tissues at time of first diagnosis. Kaplan‐Meier survival curves were analyzed to determine the relation of Hsp70 expression to the patients' prognosis.RESULTSAn Hsp70 membrane‐positive phenotype was found in 40% (colon), 37% (gastric), 43% (lower rectal), and 42% (squamous cell) of the analyzed tumor specimens. None of the corresponding normal tissues was found to be Hsp70 membrane‐positive. In patients with colon (P = .032) and gastric (P = .045) carcinomas, an Hsp70 membrane expression correlated significantly with an improved overall survival; a negative association was seen in lower rectal (P = .085) and squamous cell carcinoma (P = .048).CONCLUSIONSThe authors hypothesized that differing relations between surface expression of Hsp70 on tumor cells and clinical outcomes may reflect differences in the route of metastases. Colon and gastric carcinomas metastasize into the liver where hepatic natural killer cells may have the capacity to recognize and kill Hsp70 membrane‐positive tumor cells and thus account for a better overall survival. Cancer 2007; 110:926–35. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Patient survival by Hsp70 membrane phenotype

Pfister

Radons

Busch

et al. 2007

Cancer

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“…The intrahepatic immune environment is often associated with tolerance rather than immunity (21,22). An immunoregulatory cytokine, IL-10 is preferentially abundant in the liver (21,36,37). Such a microenvironmental factor may prevent the induction of Tim-3L on the hepatic T cells and APCs.…”

Section: Discussionmentioning

confidence: 99%

Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

Oikawa

Kamimura

Akiba

et al. 2006

The Journal of Immunology

103

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Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses. We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor- and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number, and infiltration of lymphocytes in the liver. IFN-γ expression by splenic and hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in aGVHD augmented the activation of effector T cells expressing IFN-γ or exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in the regulation of CD8+ T cells responsible for the maintenance of hepatic homeostasis and tolerance.

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“…Intrahepatic leukocytes encompass 25% of liver cells, among which resident macrophages (Kupffer cells), NK cells, NKT cells, and CD4 ϩ and CD8 ϩ T lymphocytes are highly represented (2,3). Innate lymphocytes (including NK, NKT, and some T cell subsets) are activated following recognition of modified self-Ags that reveal cellular changes such as viral infection, transformation, changes in MHC class I expression, and stressinduced proteins (4,5).…”

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confidence: 99%

Lymphocytes Support Oval Cell-Dependent Liver Regeneration

Strick‐Marchand

Masse

Weiss

et al. 2008

The Journal of Immunology

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In case of hepatic damage, the liver uses a unique regeneration mechanism through proliferation of hepatocytes. If this process is inhibited, bipotent oval stem cells proliferate and differentiate to hepatocytes and bile ducts, thus restoring liver mass. Although oval cell accumulation in the liver is often associated with inflammatory processes, the role of lymphocytes in oval cell-mediated hepatic regeneration is poorly understood. We treated wild-type and immunodeficient mice with an oval cell-inducing diet: in the absence of T cells (CD3ε−/− and Rag2−/−) there were fewer oval cells, whereas in alymphoid mice (Rag2−/−γc−/−) a strongly reduced oval cell response and higher mortality, due to liver failure, was observed. Adoptive transfer of T cells into alymphoid mice protected them from liver failure, but was insufficient to restore the oval cell response. Treatment of Rag2−/− mice with an NK cell-depleting Ab resulted in a significantly diminished oval cell response. These genetic experiments point to a major role for NK and T cells in oval cell expansion. In wild-type mice, oval cell proliferation is accompanied by an intrahepatic inflammatory response, characterized by the recruitment of Kupffer, NK, NKT, and T cells. Under these conditions, lymphocytes produce TH1 proinflammatory cytokines (IFN-γ and TNF-α) that are mitogenic for oval cells. Our data suggest that T and NK lymphocytes stimulate oval cell expansion by local cytokine secretion. This beneficial cross-talk between the immune system and liver stem cells operates under noninfectious conditions and could promote tissue regeneration following acute liver damage.

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The composition of intrahepatic lymphocytes: shaped by selective recruitment?

Cited by 82 publications

References 41 publications

Patient survival by Hsp70 membrane phenotype

Patient survival by Hsp70 membrane phenotype

Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

Lymphocytes Support Oval Cell-Dependent Liver Regeneration

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