A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load

Asquith, Becca; Mosley, Adam; Barfield, Anna; Marshall, Sara E.; Heaps, Adrian; Goon, Peter; Hanon, Emmanuel; Tanaka, Yuetsu; Taylor, Graham P.; Bangham, Charles R. M.

doi:10.1099/vir.0.80766-0

Cited by 80 publications

(105 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…After incubation with Tax-specific CTLs, on average 83% of Tax-expressing primary cells were lysed ( Figure 6B). In addition, the median fluorescent intensity (MFI) of Tax staining was significantly reduced after incubation with Tax-specific CTLs (Additional file 2), consistent with our previous finding that cells expressing high levels of Tax protein were preferentially killed [2,3]. In contrast, HBZ-specific CTLs did not kill a significant number of Tax-expressing cells; nor was any reduction in Tax MFI observed.…”

Section: Cd4supporting

confidence: 79%

See 1 more Smart Citation

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Rowan¹,

Suemori²,

Fujiwara³

et al. 2014

Retrovirology

Self Cite

View full text Add to dashboard Cite

Background: Immunogenetic evidence indicates that cytotoxic T lymphocytes (CTLs) specific for the weak CTL antigen HBZ limit HTLV-1 proviral load in vivo, whereas there is no clear relationship between the proviral load and the frequency of CTLs specific for the immunodominant antigen Tax. In vivo, circulating HTLV-1-infected cells express HBZ mRNA in contrast, Tax expression is typically low or undetectable. To elucidate the virus-suppressing potential of CTLs targeting HBZ, we compared the ability of HBZ-and Tax-specific CTLs to lyse naturally-infected cells, by co-incubating HBZ-and Tax-specific CTL clones with primary CD4 + T cells from HLA-matched HTLV-1-infected donors. We quantified lysis of infected cells, and tested whether specific virus-induced host cell surface molecules determine the susceptibility of infected cells to CTL-mediated lysis.

show abstract

Section: Cd4supporting

confidence: 79%

“…+ cells when co-cultured directly ex vivo [1], and the rate of CTL lysis of virus-expressing cells is inversely proportional to the proviral load [2,3], a clinical predictor of disease risk.…”

Section: Htlv-1-infected Autologous Cd4mentioning

confidence: 99%

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Rowan¹,

Suemori²,

Fujiwara³

et al. 2014

Retrovirology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The same uncertainty holds for the killing rate. Asquith et al (6) estimated that CTLs specific for human T-lymphotropic virus type 1 (HTLV-1)-infected cells kill no more than five target cells per day. Stinchcombe et al (89) and Wiedemann et al (97) showed that CTLs kill the target cells that they are associated with in a few minutes.…”

Section: Resultsmentioning

confidence: 99%

Understanding the Failure of CD8⁺T-Cell Vaccination against Simian/Human Immunodeficiency Virus

Boer

2007

J Virol

View full text Add to dashboard Cite

Although CD8 ؉ T cells play an important role in controlling viral infections, boosting specific CD8 ؉ T cells by prophylactic vaccination with simian immunodeficiency virus (SIV) epitopes fails to provide sterilizing immunity. Viral replication rates and viral contraction rates after the peak viremia hardly depend on the presence of memory CD8 ؉ T cells. To study these paradoxical findings, we parameterize novel mathematical models for acute SIV and human immunodeficiency virus infection. These models explain that failure of vaccination is due to the fact that effector/target ratios are too low during the viral expansion phase. Because CD8 ؉ T cells require cell-to-cell contacts, immune protection requires high effector/target ratios at the primary site of infection. Effector/target ratios become favorable for immune control at the time of the peak in the viral load when the virus becomes limited by other factors, such as the availability of uninfected target cells. At the viral set point, effector/target ratios are much higher, and perturbations of the number of CD8 ؉ effector cells have a large impact on the viral load. Such protective effector/target ratios are difficult to achieve with nucleic acid-or protein-based vaccines.

show abstract

“…In HTLV-1 infection, several studies have failed to show a consistent correlation between HTLV-1-specific CTL frequency and PVL levels (15). In fact, the rate of CD8 ϩ cell-mediated lysis of HTLV-1-infected cells in vitro (i.e., the efficiency of virus-specific CTLs) shows a significant negative correlation with PVL in vivo (35).…”

Section: Discussionmentioning

confidence: 99%

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Oliveira

Hayakawa

Schor

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11–19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8+ T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8+ T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2(11–19) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.

show abstract

A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load

Abstract: The CD8+ lymphocyte response is a main component of host immunity, yet it is difficult to quantify its contribution to the control of persistent viruses.

Cited by 80 publications

References 42 publications

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Understanding the Failure of CD8⁺T-Cell Vaccination against Simian/Human Immunodeficiency Virus

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Contact Info

Product

Resources

About

A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load

Abstract: The CD8+ lymphocyte response is a main component of host immunity, yet it is difficult to quantify its contribution to the control of persistent viruses.

Cited by 80 publications

References 42 publications

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Understanding the Failure of CD8+T-Cell Vaccination against Simian/Human Immunodeficiency Virus

High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Contact Info

Product

Resources

About

Understanding the Failure of CD8⁺T-Cell Vaccination against Simian/Human Immunodeficiency Virus