Indoleamine 2,3-Dioxygenase (IDO) Activity During the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge

Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex–peptide complexes to directly visualize antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (EBV) infection in humans. We show that massive expansion of activated, antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte antigen (HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of antigen-specific T cells fell in most donors studied, although populations of antigen-specific cells continued to be easily detectable for at least 3 yr.

Download Full-text

Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection

Journal of General Virology ◽

10.1099/vir.0.053124-0 ◽

2013 ◽

Vol 94 (7) ◽

pp. 1451-1461 ◽

Cited By ~ 34

Author(s):

Julie M. Fox ◽

Leo K. Sage ◽

Lei Huang ◽

James Barber ◽

Kimberly D. Klonowski ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Influenza Virus ◽

T Cell ◽

Virus Infection ◽

Cell Response ◽

Influenza Virus Infection ◽

T Cell Response ◽

Th17 Response ◽

Indoleamine 2,3 Dioxygenase

Influenza infection induces an increase in the level of indoleamine 2,3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate-limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-d,l-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4+ T-cells, influenza-specific CD8+ T-cells and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4+ T-cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T-cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T-cell response.

Download Full-text

Faculty Opinions recommendation of Transcriptional insights into the CD8(+) T cell response to infection and memory T cell formation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717977293.793476883 ◽

2013 ◽

Author(s):

Donna Farber ◽

Naomi Yudanin

Keyword(s):

T Cell ◽

Cell Response ◽

Cell Formation ◽

Cd8 T Cell ◽

T Cell Response ◽

Memory T Cell

Download Full-text

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

Vaccines ◽

10.3390/vaccines9060606 ◽

2021 ◽

Vol 9 (6) ◽

pp. 606

Author(s):

Giuseppe Cappellano ◽

Hugo Abreu ◽

Chiara Casale ◽

Umberto Dianzani ◽

Annalisa Chiocchetti

Keyword(s):

Immune Response ◽

T Cell ◽

Cell Response ◽

Humoral Response ◽

Cd8 T Cell ◽

T Cell Response ◽

Next Generation ◽

Emerging Viruses ◽

Whole Cells ◽

Effector Functions

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.

Download Full-text

The immune response against myelin basic protein in two strains of rat with different genetic capacity to develop experimental allergic encephalomyelitis.

Journal of Experimental Medicine ◽

10.1084/jem.141.1.72 ◽

1975 ◽

Vol 141 (1) ◽

pp. 72-81 ◽

Cited By ~ 61

Author(s):

D E McFarlin ◽

S C Hsu ◽

S B Slemenda ◽

F C Chou ◽

R F Kibler

Keyword(s):

Immune Response ◽

T Cell ◽

Experimental Allergic Encephalomyelitis ◽

Cell Response ◽

Basic Protein ◽

T Cell Response ◽

Skin Tests ◽

Allergic Encephalomyelitis ◽

Experimental Allergic

After challenge with guiena pig basic protein (GPBP) Lewis (Le) rats, which are homozygous for the immune response experimental allergic encephalomyelitis (Ir-EAE) gene, developed positive delayed skin tests against GPBP and the 43 residue encephalitogenic fragment (EF); in addition, Le rat lymph node cells (LNC) were stimulated and produced migration inhibitory factor (MIF) when incubated in vitro with these antigens. In contrast Brown Norway (BN) rats, which lack the Ir-EAE gene, did not develop delayed skin tests to EF and their LNC were not stimulated and did not produce MIF when incubated in vitro with EF. These observations indicate that the Ir-EAE gene controls a T-cell response against the EF. Le rats produced measurable anti-BP antibody by radioimmunoassay after primary challenge. Although no antibody was detectable in BN rats by radioimmunoassay, radioimmunoelectrophoresis indicated that a small amount of antibody was formed after primary immunization. After boosting intraperitoneally, both strains of rat exhibited a rise in anti-BP antibody; which was greater in Le rats. In both strains of rat the anti-BP antibody reacted with a portion of the molecule other than the EF. Since EF primarily evokes a T cell response, it is suggested that the EF portion of the BP molecule may contain a helper determinant in antibody production.

Download Full-text

The molecular basis of the memory T cell response: differential gene expression and its epigenetic regulation

Nature Reviews Immunology ◽

10.1038/nri3173 ◽

2012 ◽

Vol 12 (4) ◽

pp. 306-315 ◽

Cited By ~ 161

Author(s):

Nan-ping Weng ◽

Yasuto Araki ◽

Kalpana Subedi

Keyword(s):

Gene Expression ◽

T Cell ◽

Differential Gene Expression ◽

Epigenetic Regulation ◽

Cell Response ◽

Molecular Basis ◽

T Cell Response ◽

Memory T Cell ◽

Differential Gene

Download Full-text

Effective cancer immunotherapy by Ganoderma lucidum polysaccharide-gold nanocomposites through dendritic cell activation and memory T cell response

Carbohydrate Polymers ◽

10.1016/j.carbpol.2018.10.028 ◽

2019 ◽

Vol 205 ◽

pp. 192-202 ◽

Cited By ~ 26

Author(s):

Shulei Zhang ◽

Guibin Pang ◽

Chao Chen ◽

Jianzhong Qin ◽

Huan Yu ◽

...

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Cancer Immunotherapy ◽

Cell Response ◽

Ganoderma Lucidum ◽

Cell Activation ◽

T Cell Response ◽

Dendritic Cell Activation ◽

Memory T Cell ◽

Gold Nanocomposites

Download Full-text

The Effector T Cell Response to Influenza Infection

Current Topics in Microbiology and Immunology - Influenza Pathogenesis and Control - Volume II ◽

10.1007/82_2014_397 ◽

2014 ◽

pp. 423-455 ◽

Cited By ~ 11

Author(s):

Matthew M Hufford ◽

Taeg S Kim ◽

Jie Sun ◽

Thomas J Braciale

Keyword(s):

T Cell ◽

Cell Response ◽

Influenza Infection ◽

T Cell Response ◽

Effector T Cell

Download Full-text

Neoantigen-specific CD4+ T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000421 ◽

2020 ◽

Vol 8 (2) ◽

pp. e000421

Author(s):

Peng Peng ◽

Hongming Hu ◽

Ping Liu ◽

Lisa X Xu

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Tumor Antigen ◽

Cell Response ◽

Antitumor Immunity ◽

T Cell Response ◽

Thermal Therapy ◽

Term Survival

BackgroundTraditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.MethodsThe long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice treated with RFA or cryo-thermal therapy were coincubated with tumor antigen peptides to detect the frequency of antigen specific CD4+ and CD8+ T-cells by flow cytometry. Splenocytes were then stimulated and expanded by αCD3 or peptides and adoptive T-cell therapy experiments were performed to identify the antitumor efficacy of T-cells induced by RFA and cryo-thermal therapy. Naïve mice and tumor-bearing mice were used as control groups.ResultsLocal cryo-thermal therapy generated a stronger systematic antitumor immune response than RFA and a long-lasting antitumor immunity that protected against tumor rechallenge. In vitro studies showed that the antigen-specific CD8+ T-cell response was induced by both cryo-thermal therapy and RFA, but the strong neoantigen-specific CD4+ T-cell response was only induced by cryo-thermal therapy. Cryo-thermal therapy-induced strong antitumor immune response was mainly mediated by CD4+ T-cells, particularly neoantigen-specific CD4+ T-cells.ConclusionCryo-thermal therapy induced a stronger and broader antigen-specific memory T-cells. Specifically, cryo-thermal therapy, but not RFA, led to a strong neoantigen-specific CD4+ T-cell response that mediated the resistance to tumor challenge.

Download Full-text