CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

Killian, M. Scott; Roop, Jeremy I.; Ng, Sharon; Hecht, Frederick M.; Levy, Jay A.

doi:10.1007/s10875-009-9275-y

Cited by 11 publications

(9 citation statements)

References 47 publications

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“…The finding of decreased frequencies of CD45RA Ϫ CD27 ϩ CD8 ϩ cells in patients receiving antiretroviral therapy ( Fig. 1A and B) provides an explanation for the previously observed loss of CNAR activity in CD8 ϩ cells from these subjects (22,44). Still, differences in CD8 ϩ cell subset frequencies, as measured by flow cytometry, do not necessarily account for a loss or gain of antiviral function.…”

Section: Discussionmentioning

confidence: 66%

“…This CD8 ϩ cell noncytotoxic antiviral response (CNAR) becomes evident during the acute stage of infection (22,38), varies in magnitude among HIV-infected persons (21,35,52), and directly correlates with a healthy clinical state (3,6,7,14,25,35). Strong CNAR activity is a feature of long-term survivors (LTS) of HIV infection (3,14).…”

Section: Cd8mentioning

confidence: 99%

“…CNAR activity is also associated with resistance to HIV infection among exposed seronegative individuals (27,45). CD8 ϩ cells from uninfected persons, individuals with AIDS, and HIV-infected subjects receiving long-term antiretroviral therapy typically exhibit little or no CNAR activity (21,22,44).…”

Section: Cd8mentioning

confidence: 99%

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Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells

Killian

Johnson

Teque

et al. 2011

J Virol

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HIV replication is suppressed in vitro by a CD8 + cell noncytotoxic antiviral response (CNAR). This activity directly correlates with an asymptomatic clinical state. The objective of this study was to identify the phenotype of CD8 + cell subsets having strong CNAR activity. CD8 + cell subset frequencies and CNAR levels were measured for human immunodeficiency virus (HIV)-uninfected individuals and three groups of HIV type 1 (HIV-1)-infected individuals: asymptomatic individuals with low-level viremia (vHIV), antiretroviral-drug-treated subjects with undetectable virus levels (TxHIV), and therapy-naïve aviremic elite controllers (EC). CD8 + cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA − CD27 + and PD-1 + (CD279 + ) cells. Functional assessments of CD8 + cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA − CCR7 − CD27 + and PD-1 + CD8 + cells. T cell receptor (TCR) repertoire profiles of CD8 + cell subsets having strong CNAR activity exhibited increased perturbations in comparison to those of inactive subsets. Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8 + cells expressing PD-1 and having a transitional memory cell phenotype. The findings better describe the identity of CD8 + cells showing CNAR and should facilitate the evaluation of this important immune response in studies of HIV pathogenesis, resistance to infection, and vaccine development.

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Section: Discussionmentioning

confidence: 66%

Section: Cd8mentioning

confidence: 99%

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Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells

Killian

Johnson

Teque

et al. 2011

J Virol

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“…While evidence has indicated increased CD4 ϩ T cell counts after HAART, it has also been reported that noncytotoxic CD8 ϩ T cell anti-HIV responses may contribute significantly to immune system reconstitution by suppressing HIV replication (54). Clinical studies have demonstrated the use of the CD4/CD8 ratio as an indicator of immunocompromise in HIV-infected individuals, with high sensitivity (98%) and specificity (Ͼ98%), particularly for children Ͻ2 years of age (55,56).…”

Section: Discussionmentioning

confidence: 99%

HIV Infection and Microbial Diversity in Saliva

et al. 2014

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f Limited information is available about the effects of HIV and subsequent antiretroviral treatment on host-microbe interactions. This study aimed to determine the salivary microbial composition for 10 HIV-seropositive subjects, before and 6 months after highly active antiretroviral therapy (HAART), compared with that for 10 HIV-seronegative subjects. A conventional culture and two culture-independent analyses were used and consistently demonstrated differences in microbial composition among the three sets of samples. HIV-positive subjects had higher levels of total cultivable microbes, including oral streptococci, lactobacilli, Streptococcus mutans, and Candida, in saliva than did HIV-negative subjects. The total cultivable microbial levels were significantly correlated with CD4 ؉ T cell counts. Denaturing gradient gel electrophoresis (DGGE), which compared the overall microbial profiles, showed distinct fingerprinting profiles for each group. The human oral microbe identification microarray (HOMIM) assay, which compared the 16S rRNA genes, showed clear separation among the three sample groups. Veillonella, Synergistetes, and Streptococcus were present in all 30 saliva samples. Only minor changes or no changes in the prevalence of Neisseria, Haemophilus, Gemella, Leptotrichia, Solobacterium, Parvimonas, and Rothia were observed. Seven genera, Capnocytophaga, Slackia, Porphyromonas, Kingella, Peptostreptococcaceae, Lactobacillus, and Atopobium, were detected only in HIVnegative samples. The prevalences of Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, Granulicatella, and Atopobium were increased after HAART. In contrast, the prevalence of Aggregatibacter was significantly decreased after HAART. The findings of this study suggest that HIV infection and HAART can have significant effects on salivary microbial colonization and composition.

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“…Despite the potential to combine viral vectors, most recently published Phase I trials of new candidate HIV vaccines employ a DNA prime, adenoviral boost regime that induces only modest T cell frequencies (median IFN-g spot forming cells per million of 891 [32] and 237 [33]) or employ only a single vector [34]. The addition of a second viral vector such as a poxvirus, which is currently the best boosting vector, should further enhance T cell immunity, particularly the CD8 + T cell frequencies that are so important to HIV immunity [35]. Table 1 illustrates how the specific properties of each of the main groups of viral vectors are employed to harness their respective advantages.…”

Section: The Long-awaited Success Of Viral-vectored Vaccines In Clinimentioning

confidence: 99%

Viral vectors as vaccine platforms: deployment in sight

Rollier

Reyes-Sandoval

Cottingham

et al. 2011

Current Opinion in Immunology

187

171

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CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

Cited by 11 publications

References 47 publications

Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells

Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells

HIV Infection and Microbial Diversity in Saliva

Viral vectors as vaccine platforms: deployment in sight

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CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

Cited by 11 publications

References 47 publications

Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8+T Cells

Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8+T Cells

HIV Infection and Microbial Diversity in Saliva

Viral vectors as vaccine platforms: deployment in sight

Contact Info

Product

Resources

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Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells

Natural Suppression of Human Immunodeficiency Virus Type 1 Replication Is Mediated by Transitional Memory CD8⁺T Cells