Kupffer cells required for high affinity peptide-induced deletion, not retention, of activated CD8+ T cells by mouse liver

Kuniyasu, Yuhshi; Marfani, Suhail Mohammed; Inayat, Irteza; Sheikh, Shehzad Z.; Mehal, Wajahat Z.

doi:10.1002/hep.20153

Cited by 46 publications

(36 citation statements)

References 34 publications

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“…96 The most unique characteristic of Kupffer cells is their ability to secrete the regulatory cytokines IL-10 and TGF-b after LPS stimulation. 97 Kupffer cells can also suppress DC-mediated T-cell activation through prostaglandin (PG)E 2 , 15d-PGJ 2 and nitric oxide expression.…”

Section: -95mentioning

confidence: 99%

The liver works as a school to educate regulatory immune cells

Tian

2013

Cell Mol Immunol

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Because of its unique blood supply, the liver maintains a special local immune tolerogenic microenvironment. Moreover, the liver can impart this immune tolerogenic effect on other organs, thus inducing systemic immune tolerance. The network of hepatic regulatory cells is an important mechanism underlying liver tolerance. Many types of liver-resident antigen-presenting cells (APCs) have immune regulatory function, and more importantly, they can also induce the differentiation of circulating immune cells into regulatory cells to further extend systemic tolerance. Thus, the liver can be seen as a type of 'school,' where liver APCs function as 'teachers' and circulating immune cells function as 'students.'

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Section: -95mentioning

confidence: 99%

The liver works as a school to educate regulatory immune cells

Tian

2013

Cell Mol Immunol

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“…Following trapping there was a temporary expansion of the population of activated T cells in the liver, but the massive proliferation of T cells seen at sites of inflammation does not occur in the liver. Activated CD8 + T cells underwent an approximately 8-fold expansion in the first 48 hours after injection into the portal vein of mice (Kuniyasu et al, 2004). The expansion was followed by apoptosis and a reduction in the intrahepatic population of CD8 + T cells over the next four days.…”

Section: Deletion Of Activated T Cellsmentioning

confidence: 99%

Liver Immunobiology

Parker¹,

Picut²

2005

Toxicol Pathol

148

106

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The liver has a number of important functions in innate and adaptive immunity. Contributions to the innate (nonspecific) immune system include production of acute phase proteins, nonspecific phagocytosis of particles, nonspecific pinocytosis of molecules, and nonspecific cell killing. Hepatic involvement in innate immunity contributes to the systemic response to local inflammation, clearance of particles and soluble molecules from the circulation, and killing of invading cells such as neoplastic cells. Liver involvement in the adaptive (specific) immune system includes deletion of activated T cells, induction of tolerance to ingested and self-antigens, extrathymic proliferation of T cells, and deletion of many of the signaling and effector molecules. Hepatic involvement in adaptive immunity allows clearance of activated T cells and signaling molecules following inflammatory reactions, and promotes immunologic tolerance toward potentially antigenic proteins that are absorbed from the intestinal tract. The liver is a major site of extrathymic T cell development, which assumes increasing significance with aging in mammals. Perturbations in hepatic structure or function can result in significant ramifications in both the innate and adaptive immune systems.

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“…The liver is known for its ability to induce Ag-specific immune tolerance rather than immunity (10). Liver nonparenchymal cells, including liver sinusoidal endothelial cells (LSECs) and Kupffer cells, play a crucial role in maintaining the homeostasis of the hepatic microenvironment through induction of Ag-specific T cell tolerance (11)(12)(13). Among those different cell populations involved in the induction of hepatic tolerance, LSECs are particularly important because they are strategically located in the liver sinusoids to interact with passenger leukocytes (14).…”

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confidence: 99%

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

Liu

Jiang

et al. 2013

The Journal of Immunology

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Liver sinusoidal endothelial cells (LSECs) are unique organ-resident APCs capable of Ag cross-presentation and subsequent tolerization of naive CD8+ T cells. Under certain conditions, LSECs can switch from a tolerogenic to an immunogenic state and promote the development of T cell immunity. However, little is known about the mechanisms of LSECs to induce T cell immunity. In this study, we investigated whether functional maturation of LSECs can be achieved by TLR ligand stimulation and elucidated the mechanisms involved in LSEC-induced T cell immunity. We demonstrate that pretreatment of LSECs with palmitoyl-3-cysteine-serine-lysine-4 (P3C; TLR1/2 ligand) but not poly(I:C) (TLR3 ligand) or LPS (TLR4 ligand) reverted their suppressive properties to induce T cell immunity. Importantly, P3C stimulation caused functional maturation of Ag-presenting LSECs and enabled them to activate virus-specific CD8+ T cells. The LSEC-mediated CD8+ T cell immunity was initiated by soluble mediators, one of which was IL-12 secreted at a low but sustained level after P3C stimulation. P3C stimulation did not induce programmed death ligand 1 expression on LSECs, thereby favoring T cell proliferation and activation instead of suppression. Our data suggest that LSECs undergo maturation exclusively in response to TLR1/2 ligand stimulation and that the immunological status of LSECs was dependent upon the balance between programmed death ligand 1 and IL-12 expression. These results have implications for our understanding of liver-specific tolerance and autoimmunity and for the development of strategies to overcome T cell tolerance in situations such as chronic viral liver infections or liver cancer.

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Kupffer cells required for high affinity peptide-induced deletion, not retention, of activated CD8+ T cells by mouse liver

Cited by 46 publications

References 34 publications

The liver works as a school to educate regulatory immune cells

The liver works as a school to educate regulatory immune cells

Liver Immunobiology

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

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