Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover

  title={Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover},
  author={Jorge R. Almeida and David A. Price and Laura Papagno and Za{\"i}na Ait Arkoub and Delphine Sauce and Ethan R Bornstein and Tedi E. Asher and Assia Samri and Aur{\'e}lie Schnuriger and Ioannis D Theodorou and Dominique Costagliola and Christine Rouzioux and Henri Agut and Anne Genevi{\`e}ve Marcelin and Daniel C. Douek and Brigitte Autran and Victor Appay},
  journal={The Journal of Experimental Medicine},
  pages={2473 - 2485}
The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27… 

Figures and Tables from this paper

The link between CD8+ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate

Data emphasize the central role of the TCR as a determinant of CD8+ T-cell efficacy and demonstrate that the complexities of antigen recognition across epitope and HLA class I boundaries can confound simple relationships between TCR engagement and HIV suppression.

Persistent Survival of Prevalent Clonotypes within an Immunodominant HIV Gag-Specific CD8+ T Cell Response

Examination of Ag-specific CD8+ TCR repertoires longitudinally in a cohort of HLA-B*2705+ long-term nonprogressors with chronic HIV-1 infection suggests an antiapoptotic phenotype and the ability to cross-recognize variant epitopes contribute to clonotype longevity and selection within the peripheral memory T cell pool in the presence of persistent infection with a genetically unstable virus.

Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes

Effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes is demonstrated and strongly suggest that these 12 epitopes are strong candidates for antigens for an AIDS vaccine.

Complex T-Cell Receptor Repertoire Dynamics Underlie the CD8+ T-Cell Response to HIV-1

Data suggest a continuous bidirectional process of adaptation between HIV-1 and virus-specific CD8+ T-cell clonotypes orchestrated at the TCR-antigen interface, which provides insights into the process of coadaptation between the human immune system and a rapidly evolving lentivirus.

Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection.

The potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection are revealed.

CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

It is hypothesized that polyfunctional HIV-1-specific CD8 T cells capable of viral control are present in most patients early in infection and these cells are distinguished by their ability to secrete interleukin (IL)-2 and proliferate.

Heterogeneity in HIV Suppression by CD8 T Cells from HIV Controllers: Association with Gag-Specific CD8 T Cell Responses1

The importance of Gag responses in the antiviral potency of CD8+ T cells from HICs is suggested and it is proposed that other host mechanisms may contribute to restraining HIV infection in Hics.

Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression

Significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8 + TTE cells, both at baseline and at 12 months post-infection.



Maintenance of Large Numbers of Virus-Specific CD8+ T Cells in HIV-Infected Progressors and Long-Term Nonprogressors

It is demonstrated that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease and suggested that other qualitative parameters of the CD8- T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.

Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression.

HIV-1-specific CD4 Th1 responses combined with IgG2 antibodies and IFN- gamma -producing CD4Th1 cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1 -specific CD 4 Th1 or CD8 T cell proliferation.

Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection

Overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection, and a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8+ T-cell frequency.

HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.

The quality of the HIV-specific CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy.

PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression

The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.

Oligoclonal Expansions of CD8+ T Cells in Chronic HIV Infection Are Antigen Specific

Tetrameric major histocompatibility complex–peptide complexes are used in conjunction with anti-BV chain–specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8+ T cells are HIV specific in vivo.

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load

A comprehensive analysis of the 160 dominant CD8+ T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa suggested the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection.

HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1

It is demonstrated that a subset of CD8+ T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized.

Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection

It is shown that the activation level and the differentiation state of T-cells are closely related and may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system.