The effects of polyinosinic: Polycytidylic acid (pl:C) on the GVH reaction: Immunopathological observations

Peres, Amos; Seemayer, Thomas A.; Lapp, Wayne S.

doi:10.1016/0090-1229(86)90209-6

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Hence, TLR ligands can have dual immunomodulating properties, and the suppressive nature of them could be damaging (impairing antiviral responses) or beneficial (preventing immune disorders). Historical data demonstrating the dual immuno-modulating properties of poly(I:C) include a classic model of graft-versus-host disease (38,39) and autoimmune diabetes (13,18). Collectively, these results suggest that poly(I:C), and perhaps many other TLR ligands, may be able to both promote and dampen an immune response based on the timing, the magnitude, or the type of inflammation induced.…”

Section: Discussionmentioning

confidence: 73%

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Ngoi

Rose

Ménoret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The synthetic double-stranded RNA poly(I:C) is commonly used as an adjuvant to boost CD8 T-cell function; however, polyinosinic:polycytidylic acid [poly(I:C)] can also suppress autoimmune disease. The mechanism by which a single adjuvant achieves two distinct immunoregulatory roles is unknown. Although it is clear that coadministration of poly(I:C) with antigen elicits strong adjuvant effects in mice, we found that poly(I:C) injection before antigen substantially reduced antigen-dependent CD8 T-cell responses. Notably, CD8 T cells sensitized in poly(I:C)-pretreated mice failed to fully up-regulate IL-33R (ST2), which led to impaired T-cell receptor-independent responses to IL-33. In contrast, nonsensitized effector CD8 T cells responded robustly to IL-33 using a two-signal cytokine mechanism. During an acute lung response to Staphylococcus aureus enterotoxin, peripheral injection of poly(I:C) manifested a suppressive process by inhibiting the differentiation of both antigen- and IL-33–responsive CD8 effectors systemically. These findings highlight that early exposure to double-stranded RNA reverses its role as an adjuvant and, importantly, prevents IL-33R up-regulation on CD8 effector T cells to dampen inflammation.

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Section: Discussionmentioning

confidence: 73%

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Ngoi

Rose

Ménoret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Protection has been observed against influenza virus [90], Rift Valley fever virus [16], rabies virus [97], Punta Toro virus [98], Herpes simplex virus type 2 [99], western equine encephalitis virus [100], Venezuelan equine encephalomyelitis virus [101], yellow fever virus [102], SARS-Co-V [81], RSV [103], white spot syndrome virus and Taura syndrome virus [96]. Poly (IC) has also been shown, through its effects on NK cells, to eliminate the histological lesions of graft-versus-host disease in mice [104].…”

Section: Drugs Targeting Tlr3mentioning

confidence: 99%

Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections

Christopher¹

2011

aiamc

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Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.

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“…In primates, poly (ICLC) is effective against yellow fever virus [ 43 ], Venezuelan equine encephalomyelitis virus (VEEV) [ 44 ] and rabies virus [ 39 ]. Poly(IC) has also been shown, through its effects on NK cells, to eliminate the histological lesions of graft-versus-host disease in mice [ 45 ]. Ampligen, a mismatched double-stranded RNA currently under development by Hemispherx Biopharma in the U.S.A., acts by inducing IFN production (immunomodulator) and by activating an intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral).…”

Section: Tlr3 Agonists: Dsrnamentioning

confidence: 99%

Broad-Spectrum Drugs Against Viral Agents

Christopher

Wong

2008

IJMS

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Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.

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The effects of polyinosinic: Polycytidylic acid (pl:C) on the GVH reaction: Immunopathological observations

Cited by 4 publications

References 33 publications

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness

Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections

Broad-Spectrum Drugs Against Viral Agents

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