IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Liu, Xiao Song; Xu, Yixin; Hardy, Lani; Khammanivong, Vithagna; Zhao, Weiming; Fernando, Germain J. P.; Leggatt, Graham R.; Frazer, Ian H.

doi:10.4049/jimmunol.171.9.4765

Cited by 46 publications

(33 citation statements)

References 48 publications

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“…Type I IFN has been reported to alter regulatory T cell activity, which impacts CD8 + T cell function [37], [38], and decreased regulatory T cell levels augment WNV-specific CD8 + T cell responses [39]. However, we observed no difference in the percentage or numbers of CD4 + CD25 + FoxP3 + cells at day 9 in the blood (data not shown) or spleen ( P >0.6), when MAR1-5A3 or control GIR-208 MAb was administered at day 4 after WNV-NY infection ( Figure S3 ).…”

Section: Resultsmentioning

confidence: 99%

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A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

et al. 2011

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A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3 -/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event.

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Section: Resultsmentioning

confidence: 99%

“…Within five days of MAR1-5A3 treatment, serum levels of IFN-γ, TNF-α, and IL-12 p40 were reduced significantly ( P <0.01) and IL-10 was elevated ( P <0.02). The increased level of IL-10 in mice treated with the blocking type I IFN MAb may be particularly relevant as IL-10 negatively impacts CD8 + T cell activation and function [37], [38].…”

Section: Resultsmentioning

confidence: 99%

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

et al. 2011

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“…There were evidences showing that humorally immunogenic carriers jeopardize the potency of their CTL vaccine payloads. (15–17) Therefore, we sought to use humorally tolerant ELPs as CTL vaccine carriers. Among reported ELPs, a few have been confirmed as immune tolerant while others have been proven immunogenic.…”

Section: Introductionmentioning

confidence: 99%

Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers

Cho

Dong²,

Parent

et al. 2015

Journal of Drug Targeting

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Background Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers. Purpose We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs. Results Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells and enhanced vaccine-induced CTL responses. Discussion A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines. Conclusion It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.

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“…HIV, from the immune control [4,6]. For CD8 + T cell responses this mechanism is mediated by the production of IL-10, suppressing the generation of new effector CD8 + cells secreting γ-IFN [5].…”

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confidence: 99%

Suppression of Primary Allogenic Response by CD8+ Memory Cells

et al. 2005

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Immune response to allogenic tumor cells is associated with the appearance of long-living CD8+ memory cells capable of rapid restimulation and lysis of tumor cells in case of repeated injection of these cells. In order to acquire the effector function, allorestricted memory cells need antigen restimulation for 2 days, which is a specific feature of central memory cell population. These cells can suppress proliferation of naive splenocytes in vitro. In mixed lymphocyte cultures containing memory cells, antigen stimulation induces more intensive IL-10 production and deeper suppression of IL-2 production in comparison with cultures containing naive cells. The conditions for activation of naive cells during secondary immune response are not optimal.

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IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Cited by 46 publications

References 48 publications

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers

Suppression of Primary Allogenic Response by CD8+ Memory Cells

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