Impact of antigen expression kinetics on the effectiveness of HIV‐specific cytotoxic T lymphocytes

@article{Baalen2002ImpactOA,
  title={Impact of antigen expression kinetics on the effectiveness of HIV‐specific cytotoxic T lymphocytes},
  author={Carel A. van Baalen and Christophe Guillon and Minus Van Baalen and Esther J Verschuren and Patrick H. M. Boers and Albert D.M.E. Osterhaus and Rob A Gruters},
  journal={European Journal of Immunology},
  year={2002},
  volume={32}
}
Recent studies indicate that the time required for virus‐infected cells to become vulnerable for the activity of CTL is of significance for the capacity of CTL to control ongoing viral reproduction. To investigate whether this applies to the effectiveness of HIV‐1‐specific CTL, we measured virus production in cultures containing CD4+ T cells inoculated with HIV at low multiplicity of infection, and CTL directed against an early protein, Rev, or a late protein, RT. The Rev‐specific CTL prevented… 
View on Wiley
snv.jussieu.fr
85 Citations
Highly Influential Citations
3
Background Citations
29
Methods Citations
1
Results Citations
3

85 Citations

Citation Type

Citation Type

Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection
TLDR
It is suggested that the majority of CTL-mediated killing could occur during the viral eclipse phase, and that the killing of virus-producing cells could be substantially lower at later stages due to MHC-I-down-regulation.
Impacts of Epitope Expression Kinetics and Class I Downregulation on the Antiviral Activity of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes
TLDR
Two determinants of CTL antiviral efficiency are investigated by manipulating HIV-1 and measuring the effects on CTL suppression of viral replication in acutely infected cells, indicating that both the timing of epitope expression and the reduction of class I have profound effects on the ability of C TL to suppress HIV- 1 replication in acute infected cells.
Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes.
TLDR
Results suggest that whereas Gag-specific CTLs are more likely to recognize infected cells before Nef-mediated HLA-I down-regulation, this varies depending on the specific epitope and virus inoculum, but this property is not unique to Gag.
How Many Human Immunodeficiency Virus Type 1-Infected Target Cells Can a Cytotoxic T-Lymphocyte Kill?
TLDR
Estimates that on average CTLs can kill from 0.7 to 3 infected target cells per day are demonstrated, compatible with the observed decline in viremia after primary infection being primarily a consequence of CTL activity and have interesting implications for vaccine design.
CTL quality and the control of human retroviral infections
  • C. Bangham
  • Biology
    European journal of immunology
  • 2009
TLDR
Differences in anti‐viral CTL efficiency or “quality” at the single‐cell level are critical in determining the efficacy of the host response to viruses.
Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
TLDR
It is proposed that critical CTL densities can be better estimated either using quantitative models incorporating virus life histories or with in vivo assays using virus-infected cells rather than peptide-pulsed targets.
Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response
TLDR
Evaluation of the extent and kinetics of HIV-1 escape from >40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication.
Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China
TLDR
The data demonstrate the prominent role of Gag-specific CTL responses in disease control as well as an association between HLA-A*30/B*13/Cw*06 haplotype and lower viral loads that was probably due to restricted GAG-specificCTL responses.
Nef interference with HIV-1-specific CTL antiviral activity is epitope specific.
TLDR
Examination of the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins suggests that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nf in vivo and suggest a benefit of promoting HLA -C- restricted CTLS for immunotherapy or vaccine development.
HIV-1 Gag Cytotoxic T Lymphocyte Epitopes Vary in Presentation Kinetics Relative to HLA Class I Downregulation
TLDR
Data demonstrate that epitope presentation kinetics play an important role in CTL antiviral efficiency, that Gag epitopes are not uniformly presented early, and that the epitope context can play a major role in presentation Kinetics.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 51 REFERENCES
Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection.
TLDR
It is concluded that in HIV type 1 infection, CTL-mediated lysis can reduce virus load by limiting virus production, with small effects on the half-life of infected cells.
Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes
TLDR
It is indicated that HIV-1-specific CTL can efficiently lyse HIV- 1-infected CD4+ cells and suggest that the partial downregulation of class I molecules in infected cells does not significantly affect recognition by CTL.
Kinetics of Antiviral Activity by Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes (CTL) and Rapid Selection of CTL Escape Virus In Vitro
TLDR
Analysis of antiviral activity of a CD8+ cytotoxic T-lymphocyte (CTL) clone directed against a newly identified HLA-B14-restricted epitope showed that infected cells became susceptible to CTL-mediated lysis before peak virus production but after the onset of progeny virus release, suggesting a model in which CTLs can interfere with viral protein expression during the eclipse phase via noncytolytic mechanisms.
A functional and kinetic comparison of antiviral effector and memory cytotoxic T lymphocyte populations in vivo and in vitro
TLDR
It is found that CTL from naive and memory mice perform considerably less well and can not fulfill the limiting time requirements for immediate antiviral protection, illustrating how critical time limitations are for CTL to mediate early control of a dynamic virus infection in vivo.
HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes
TLDR
It is found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed and Nef protected infected cells by reducing the epitope density on their surface.
Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.
TLDR
A remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia
TLDR
It is shown that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.
Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS.
TLDR
It is shown in twelve HIV-1-infected individuals that detection of Rev-specific CTL precursors (CTLp) early in the asymptomatic stage, as well as detection ofRev- and Tat- specific CTLp later during follow-up, inversely correlate with rapid disease progression, in agreement with the hypothesis that CTL against proteins that are important for early viral transcription and translation are of particular importance in protection from rapid Disease progression.
Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection
TLDR
Examination of virus-specific cytotoxic T lymphocytes, T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy concludes that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population.
CD8+ cells in human immunodeficiency virus type I pathogenesis: cytolytic and noncytolytic inhibition of viral replication.
...
1
2
3
4
5
...