scholarly journals Combination of TLR1/2 and TLR3 ligands enhances CD4+ T cell longevity and antibody responses by modulating type I IFN production

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Bo Ryeong Lee ◽  
Soo Kyung Jeong ◽  
Byung Cheol Ahn ◽  
Byeong-Jae Lee ◽  
Sung Jae Shin ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Type I ◽  
Type I Ifn ◽  
Cell Longevity

scholarly journals Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T Cell Homeostasis

2014 ◽  
Vol 10 (3) ◽  
pp. e1003976 ◽  
Author(s):  
Cecile Le Saout ◽  
Rebecca B. Hasley ◽  
Hiromi Imamichi ◽  
Lueng Tcheung ◽  
Zonghui Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Exposure ◽  
Cd4 T Cell ◽  
Type I ◽  
Type I Ifn ◽  
T Cell Homeostasis ◽  
Cell Homeostasis

scholarly journals USP18 is a significant driver of memory CD4 T-cell reduced viability caused by type I IFN signaling during primary HIV-1 infection

2019 ◽  
Vol 15 (10) ◽  
pp. e1008060 ◽  
Author(s):  
Xavier Dagenais-Lussier ◽  
Hamza Loucif ◽  
Hugo Cadorel ◽  
Juliette Blumberger ◽  
Stéphane Isnard ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Type I ◽  
Type I Ifn ◽  
Hiv 1

scholarly journals Interferons and HIV Infection: The Good, the Bad, and the Ugly

2016 ◽  
Vol 1 (1) ◽  
pp. 107 ◽  
Author(s):  
Netanya Sandler Utay ◽  
Daniel C. Douek
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Systemic Infection ◽  
Type I Interferons ◽  
Cd4 T Cell ◽  
Type I ◽  
Hiv Disease ◽  
Type I Ifn ◽  
Cell Recovery ◽  
Type I Ifns

Whether type I interferons (IFNs) hinder or facilitate HIV disease progression is controversial. Type I IFNs induce the production of restriction factors that protect against mucosal HIV/SIV acquisition and limit virus replication once systemic infection is established. However, type I IFNs also increase systemic immune activation, a predictor of poor CD4+ T-cell recovery and progression to AIDS, and facilitate production and recruitment of target CD4+ T cells. In addition, type I IFNs induce CD4+ T-cell apoptosis and limit antigen-specific CD4+ and CD8+ T-cell responses. The outcomes of type I IFN signaling may depend on the timing of IFN-stimulated gene upregulation relative to HIV exposure and infection, local versus systemic type I IFN-stimulated gene expression, and the subtype of type I IFN evaluated. To date, most interventional studies have evaluated IFNa2 administration largely in chronic HIV infection, and few have evaluated the effects on tissues or the HIV reservoir. Thus, whether the effect of type I IFN signaling on HIV disease is good, bad, or so complicated as to be ugly remains a topic of hot debate.

scholarly journals Type I IFN Sensing by cDCs and CD4+ T Cell Help Are Both Requisite for Cross-Priming of AAV Capsid-Specific CD8+ T Cells

2020 ◽  
Vol 28 (3) ◽  
pp. 758-770 ◽  
Author(s):  
Jamie L. Shirley ◽  
Geoffrey D. Keeler ◽  
Alexandra Sherman ◽  
Irene Zolotukhin ◽  
David M. Markusic ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Type I ◽  
Type I Ifn ◽  
Cd4 T Cell Help ◽  
T Cell Help

scholarly journals Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Norzawani Buang ◽  
Lunnathaya Tapeng ◽  
Victor Gray ◽  
Alessandro Sardini ◽  
Chad Whilding ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Mitochondrial Abnormalities

AbstractThe majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.

scholarly journals IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection

2014 ◽  
Vol 7 (5) ◽  
pp. 1151-1164 ◽  
Author(s):  
A Jayaraman ◽  
D J Jackson ◽  
S D Message ◽  
R M Pearson ◽  
J Aniscenko ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Type I ◽  
Type I Ifn ◽  
Cell Responses ◽  
Rhinovirus Infection

scholarly journals Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
Author(s):  
Spencer W. Stonier ◽  
Andrew S. Herbert ◽  
Ana I. Kuehne ◽  
Ariel Sobarzo ◽  
Polina Habibulin ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Ebola Virus ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

EXTH-77. POLIO VIROTHERAPY OF MURINE BRAIN TUMORS INDUCES MICROGLIA PROLIFERATION AND INFLAMMATION THAT IS POTENTIATED BY IMMUNE CHECKPOINT BLOCKADE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi181-vi181
Author(s):  
Yuanfan Yang ◽  
Michael Brown ◽  
Kevin Stevenson ◽  
Giselle lopez ◽  
Reb Kornahrens ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Cd8 T Cell ◽  
Gene Set Enrichment Analysis ◽  
Type I ◽  
Acute Type ◽  
Type I Ifn ◽  
Term Survival

Abstract Immunotherapy with polio:rhinovirus recombinant (PVSRIPO) has shown evidence of efficacy in a phase I clinical trial for recurrent GBM, resulting in durable radiographic responses and 21% long-term survival at 36 months. Ongoing research aims to enhance the clinical response rate by resolving the mechanisms of action and therapy resistance in vivo, thereby devising more effective therapies. Mouse glioma (CT2A) cells were intracranially implanted (day 0) in transgenic mice carrying poliovirus receptor CD155, and treated with intratumor PVSRIPO (5×105 pfu; day 6) to dissect early and late events following therapy. A blinded pathological review of 45 post-treatment tumors was performed. On day 8, a histological response, featured by tumor dissociation and shrinkage, with inflammation and microglia enrichment in the treated hemisphere, was common in PVSRIPO group (6/7) compared to controls (0/4). However, the response rate fell over time (7/12 on day 12; 1/7 on day 15) and the therapy was overcome by aggressive tumor regrowth. RNAseq was performed and Gene Set Enrichment Analysis of the tumor microenvironment revealed an acute type-I interferon (IFN)-related inflammation, correlating with the histological findings of profound proinflammatory engagement of microglia (Iba1+) widespread in the treated hemisphere. Microglia proliferation (Ki67+) was observed in the treated hemisphere, likely resulting from PVSRIPO infection, in CT2A and B16 intracranial models. This suggests an association of adaptive antitumor immunity—elicited by immediate intratumor type-I IFN-dominant inflammation—with tumor regression. Thus, buttressing type-I IFN directed antitumor CD8+T cell immunity, e.g. with blockade of the PD1:PD-L1 immune checkpoint, might contribute to tumor remission. Indeed, combination therapy with αPD-L1 antibody in the CT2A model showed longer median survival and higher long-term remission rate compared to monotherapy alone; CD8 T cell depletion can completely abrogate this efficacy with this therapy combination, confirming the role of anti-tumor immunity in this approach.

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