Characterization of Natural Killer Cells in Tamarins: A Technical Basis for Studies of Innate Immunity

Yoshida, Tomoyuki; Saito, Akatsuki; Iwasaki, Yoshiaki; Iijima, Sayuki; Kurosawa, Tohru; Katakai, Yuko; Yasutomi, Yasuhiro; Reimann, Keith A.; Hayakawa, Toshiyuki; Akari, Hirofumi

doi:10.3389/fmicb.2010.00128

Cited by 9 publications

(8 citation statements)

References 29 publications

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“…Moreover, polyfunctional NK cells have been associated with resistance to infection in HCVexposed health care workers (36). Although recent data from our lab and others have characterized marmoset NK cells and found them to be highly similar to those in humans (37,38), the reciprocal effects of GBV-B infection and NK cells are unknown.…”

mentioning

confidence: 88%

Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection

Manickam

Rajakumar

Wachtman

et al. 2016

J Virol

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Despite its importance in shaping adaptive immune responses, viral clearance, and immune-based inflammation, tissue-specific innate immunity remains poorly characterized for hepatitis C virus (HCV) infection due to the lack of access to acutely infected tissues. In this study, we evaluated the impact of natural killer (NK) cells and myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells on control of virus replication and virus-induced pathology caused by another, more rapidly resolving hepacivirus, GB virus B (GBV-B), in infections of common marmosets. High plasma and liver viral loads and robust hepatitis characterized acute GBV-B infection, and while viremia was generally cleared by 2 to 3 months postinfection, hepatitis and liver fibrosis persisted after clearance. Coinciding with peak viral loads and liver pathology, the levels of NK cells, mDCs, and pDCs in the liver increased up to 3-fold. Although no obvious numerical changes in peripheral innate cells occurred, circulating NK cells exhibited increased perforin and Ki67 expression levels and increased surface expression of CXCR3. These data suggested that increased NK cell arming and proliferation as well as tissue trafficking may be associated with influx into the liver during acute infection. Indeed, NK cell frequencies in the liver positively correlated with plasma (R ‫؍‬ 0.698; P ‫؍‬ 0.015) and liver (R ‫؍‬ 0.567; P ‫؍‬ 0.057) viral loads. Finally, soluble factors associated with NK cells and DCs, including gamma interferon (IFN-␥) and RANTES, were increased in acute infection and also were associated with viral loads and hepatitis. Collectively, the findings showed that mobilization of local and circulating innate immune responses was linked to acute virus-induced hepatitis, and potentially to resolution of GBV-B infection, and our results may provide insight into similar mechanisms in HCV infection. IMPORTANCEHepatitis C virus (HCV) infection has created a global health crisis, and despite new effective antivirals, it is still a leading cause of liver disease and death worldwide. Recent evidence suggests that innate immunity may be a potential therapeutic target for HCV, but it may also be a correlate of increased disease. Due to a lack of access to human tissues with acute HCV infection, in this study we evaluated the role of innate immunity in resolving infection with a hepacivirus, GBV-B, in common marmosets. Collectively, our data suggest that NK cell and DC mobilization in acute hepacivirus infection can dampen virus replication but also regulate acute and chronic liver damage. How these two opposing effects on the host may be modulated in future therapeutic and vaccine approaches warrants further study. H epatitis C virus (HCV) infection has become a global health epidemic, with the virus infecting more than 170 million people worldwide (1) and resulting in 350,000 HCV-related liver disease deaths each year (2). HCV infection results in the following two disparate manifestations: (i) an acute, self-resolving infection and (ii) a chron...

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confidence: 88%

Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection

Manickam

Rajakumar

Wachtman

et al. 2016

J Virol

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“…Using our model, we investigated the roles of NK cells in vivo against DENV infection, which remains to be elucidated in several aspects. We previously reported that almost complete in vivo depletion of CD16 + NK subpopulation was not able to completely remove the NK-mediated cytotoxic activity in tamarins [29]. In this study, despite a transient but substantial reduction in CD16 + NK cell number following 3G8 treatment in tamarins, DENV replication was comparable to that in monkeys with the control mAb.…”

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confidence: 46%

“…highly permissive to DENV infection [22]. The New World monkeys, being nonhuman 90 primates are considered to have a similar immune system to humans [28,29]. The 91 present study was initiated to investigate the role of NK cells in controlling DENV 92 during primary infection in our nonhuman primate model.…”

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confidence: 99%

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CD16+ natural killer cells play a limited role against primary dengue virus infection in tamarins

et al. 2011

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CD16 is a major molecule expressed on NK cells. To directly assess the role of natural killer (NK) cells in dengue virus (DENV) infection in vivo, CD16 antibody-treated tamarins were inoculated with a DENV-2 strain. This resulted in the transient depletion of CD16(+) NK cells, whereas no significant effects on the overall levels or kinetics of plasma viral loads and antiviral antibodies were observed in the treated monkeys when compared to control monkeys. It remains elusive whether the CD16(-) NK subpopulation could play an important role in the control of primary DENV infection.

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“…Flow cytometry was performed as previously described with a slight modification [22]. A previously established mouse anti-marmoset CD8 mAb named 6F10 was used [7].…”

Section: Flow Cytometrymentioning

confidence: 99%

Efficient in vivo depletion of CD8+ T lymphocytes in common marmosets by novel CD8 monoclonal antibody administration

Yoshida¹,

Suzuki²,

Iwasaki³

et al. 2013

Immunology Letters

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In order to directly demonstrate the roles of CD8(+) T lymphocytes in non-human primates, in vivo depletion of the CD8(+) T cells by administration of a CD8-specific monoclonal antibody (mAb) is one of the crucial techniques. Recently, the common marmoset (Callithrix jacchus), which is classified as a New World monkey, has been shown useful as an experimental animal model for various human diseases such as multiple sclerosis, Parkinson's disease and a number of infectious diseases. Here we show that an anti-marmoset CD8 mAb 6F10, which we have recently established, efficiently depletes the marmoset CD8(+) T lymphocytes in vivo, i.e., the administration of 6F10 induces drastic and specific reduction in the ratio of the CD8(+) T cell subset for at least three weeks or longer. Our finding will help understand the pivotal role of CD8(+) T cells in vivo in the control of human diseases.

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Characterization of Natural Killer Cells in Tamarins: A Technical Basis for Studies of Innate Immunity

Cited by 9 publications

References 29 publications

Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection

Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman Primate Model of Hepacivirus Infection

CD16+ natural killer cells play a limited role against primary dengue virus infection in tamarins

Efficient in vivo depletion of CD8+ T lymphocytes in common marmosets by novel CD8 monoclonal antibody administration

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