Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells
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{"title"=>"Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Selena", "last_name"=>"Viganò", "scopus_author_id"=>"53865661100"}, {"first_name"=>"Felicitas", "last_name"=>"Bellutti Enders", "scopus_author_id"=>"55315088000"}, {"first_name"=>"Isabelle", "last_name"=>"Miconnet", "scopus_author_id"=>"6603873737"}, {"first_name"=>"Cristina", "last_name"=>"Cellerai", "scopus_author_id"=>"8643288300"}, {"first_name"=>"Anne Laure", "last_name"=>"Savoye", "scopus_author_id"=>"55613063900"}, {"first_name"=>"Virginie", "last_name"=>"Rozot", "scopus_author_id"=>"35198870300"}, {"first_name"=>"Matthieu", "last_name"=>"Perreau", "scopus_author_id"=>"22942018700"}, {"first_name"=>"Mohamed", "last_name"=>"Faouzi", "scopus_author_id"=>"25421048600"}, {"first_name"=>"Khalid", "last_name"=>"Ohmiti", "scopus_author_id"=>"35737799300"}, {"first_name"=>"Matthias", "last_name"=>"Cavassini", "scopus_author_id"=>"6603031055"}, {"first_name"=>"Pierre Alexandre", "last_name"=>"Bart", "scopus_author_id"=>"7003826360"}, {"first_name"=>"Giuseppe", "last_name"=>"Pantaleo", "scopus_author_id"=>"34571962300"}, {"first_name"=>"Alexandre", "last_name"=>"Harari", "scopus_author_id"=>"7006247495"}], "year"=>2013, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"23853580", "sgr"=>"84883757712", "scopus"=>"2-s2.0-84883757712", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "doi"=>"10.1371/journal.ppat.1003423", "pui"=>"369919414", "issn"=>"15537366"}, "id"=>"79b11dcf-41a1-3545-8807-75e84b7da1ae", "abstract"=>"The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.", "link"=>"http://www.mendeley.com/research/rapid-perturbation-viremia-levels-drives-increases-functional-avidity-hivspecific-cd8-t-cells", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>7, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>3, "Social Sciences"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1111474"], "description"=>"<p><b>A.</b> Representative examples of functional avidity of HIV-specific CD8 T-cell responses in patients with acute (PHI-B-09; circles), chronic progressive (CP-B-08; squares) or chronic non-progressive (LTNP-2082; triangles) infection after stimulation with decreasing concentrations of B*0801-<sub>EIYKRWII</sub> peptides. The dashed line corresponds to half of the maximal response allowing the extrapolation of the 50% effect concentration (EC<sub>50</sub>). <b>B.</b> Cumulative analysis of the functional avidity of HIV-specific CD8 T cells during acute (PHI-B), untreated chronic progressive (CP-B) and non-progressive infection (LTNP). Medians and interquartile ranges are shown and each point represents one HIV-specific CD8 T-cell response. <b>C.</b> Cumulative analysis of the frequency of HIV-specific CD8 T cells during acute (PHI-B), untreated chronic progressive (CP-B) and non-progressive infection (LTNP). <b>D.</b> Functional avidity of HIV-specific CD8 T-cell responses against common optimal epitopes recognized by patients with acute (PHI-B), chronic progressive (CP-B) or not progressive (LTNP) infections. The red line (right panel) shows the functional avidity of B*2705-<sub>KRWIILGLNK</sub> (KK10)-specific CD8 T-cell response.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "avidity", "hiv-specific", "cd8", "t-cell"], "article_id"=>739772, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_avidity_of_HIV_specific_CD8_T_cell_responses_/739772", "title"=>"Functional avidity of HIV-specific CD8 T-cell responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111475"], "description"=>"<p><b>A.</b> Comparison of the magnitude (left panel) and functional avidity (right panel) of HIV-specific CD8 T-cell responses measured during acute infection (PHI-B) between responses which remained detectable (referred to as “maintained”) and those which became undetectable (referred to as “lost”) after one year of ART. Seventeen HIV-specific CD8 T-cell responses which were absent at baseline and developed during ART are also shown. <b>B.</b> Longitudinal matched-paired analysis of the functional avidity of HIV-specific CD8 T-cell responses measured before (-B) or after (-T1Y) 1 year of ART in patients with acute (PHI) or chronic progressive (CP) HIV infection. <b>C.</b> Functional avidity of independent HIV-specific CD8 T-cell responses detected in untreated (-B) or treated (-T1Y) patients with acute (PHI) or chronic progressive (CP) HIV infection. <b>D.</b> Functional avidity of HIV-specific CD8 T cells from patients with acute (PHI) or chronic progressive (CP) both after one year of ART (T1Y). <b>E.</b> Functional avidity of HIV-specific CD8 T-cell responses against common optimal epitopes recognized either by patients treated for 1 year since acute infection (PHI-T1Y) or treated for 1 year since chronic progressive infection (CP-T1Y).</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "avidity", "hiv-specific", "cd8", "t-cell", "responses"], "article_id"=>739773, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_functional_avidity_of_HIV_specific_CD8_T_cell_responses_after_one_year_of_ART_/739773", "title"=>"Analysis of the functional avidity of HIV-specific CD8 T-cell responses after one year of ART.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111476"], "description"=>"<p>Analysis of the functional profile (<b>A</b>), of the expression of CD27 and CD28 (<b>B</b>) and of the expression of 2B4, CD160 and PD-1 (<b>C</b>) in HIV-specific CD8 T cells in patients with acute (PHI-B), untreated chronic progressive (CP-B) or non-progressive (LTNP) HIV infection. Representative examples of the distinct flow cytometry panels are shown in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423.s001\" target=\"_blank\">Fig. S1B</a>-D. Regarding the functional profile (<b>A</b>), although TNF-α was detected, analyses are restricted to the expression of IFN-γ, IL-2 and perforin for clarity. All possible combinations of the distinct markers are shown on the <i>x</i> axis, whereas the percentages of the distinct cell subsets within virus-specific CD8 T cells are shown on the <i>y</i> axis. The pie charts summarize the data, and each slice corresponds to a certain combination of molecules. Colors in the pie charts are based on the colored boxes at the bottom of the panel.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "co-stimulatory", "molecules", "co-inhibitory", "receptors", "hiv-specific", "cd8", "t-cell", "responses", "acute", "hiv"], "article_id"=>739774, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_profile_and_expression_of_co_stimulatory_molecules_and_of_co_inhibitory_receptors_of_HIV_specific_CD8_T_cell_responses_during_acute_and_chronic_HIV_infections_/739774", "title"=>"Functional profile and expression of co-stimulatory molecules and of co-inhibitory receptors of HIV-specific CD8 T-cell responses during acute and chronic HIV infections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111477"], "description"=>"<p>Associations between the functional avidity of HIV-specific CD8 T-cell responses and the frequency of HIV-specific CD8 T cells co-expressing CD28 and CD27 (<b>A</b>) or PD-1, 2B4 and CD160 (<b>B</b>).</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "avidity", "hiv-specific", "cd8", "t-cell", "responses", "immunological"], "article_id"=>739775, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_functional_avidity_of_HIV_specific_CD8_T_cell_responses_and_other_immunological_parameters_/739775", "title"=>"Associations between functional avidity of HIV-specific CD8 T-cell responses and other immunological parameters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111479"], "description"=>"<p><b>A.</b> Longitudinal analysis of the CD4 T-cell counts and HIV viremia of 2 representative HIV-infected patients (#1017 and #1023) treated with ART since acute infection. Patient #1017 remained on ART, whereas patient #1023 spontaneously interrupted ART after 119 weeks (orange box). <b>B.</b> Functional profiles of B*0702-<sub>GPGHKARVL</sub>-specific CD8 T cells from patients #1017 and #1023 analyzed at two distinct time-points corresponding to weeks 48 and 300 (identified by the arrows in A). <b>C.</b> Cumulative analysis of the functional profile of HIV-specific CD8 T-cell responses on the basis of the expression of IFN-γ, IL-2 and perforin in patients with acute (PHI) infection after one year of ART (-T1Y) and after either treatment interruption (-ATI) or after five years of ART (-T5Y). Matched-paired HIV-specific CD8 T-cell responses are considered for the comparison between T1Y and ATI or between T1Y and T5Y. Although TNF-α was also detected, analysis is restricted to the expression of IFN-γ, IL-2 and perforin for clarity. All possible combinations of IFN-γ, IL-2 and perforin are shown on the <i>x</i> axis, whereas the percentages of the distinct cell subsets within HIV-specific CD8 T cells are shown on the <i>y</i> axis. The pie charts summarize the data, and each slice corresponds to a certain combination of functions. Colors in the pie charts are based on the colored boxes at the bottom of the panel. <b>D.</b> PD-1 expression in B*0702-<sub>GPGHKARVL</sub>-specific CD8 T cells in patients #1017 and #1023 measured at the two time-points identified with arrows in A. <b>E.</b> Mean fluorescence intensity (MFI) of PD-1 expression in HIV-specific CD8 T cells measured in patients with acute (PHI) HIV infection after 1 year of ART (-T1Y) and after either treatment interruption (-ATI, left panel) or after five years of ART (-T5Y, right panel). <b>F.</b> Proportion of PD-1<sup>+</sup>2B4<sup>+</sup>CD160<sup>+</sup> cells in B*0702-<sub>GPGHKARVL</sub>-specific CD8 T cells in patients #1017 and #1023 measured at the two time-points identified with arrows in A. <b>G.</b> Proportion of PD-1<sup>+</sup>2B4<sup>+</sup>CD160<sup>+</sup> cells in HIV-specific CD8 T cells measured in patients with acute (PHI) HIV infection after 1 year of ART (-T1Y) and after either treatment interruption (-ATI, left panel) or after five years of ART (-T5Y, right panel).</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "hiv-specific", "cd8", "cells", "patients", "experiencing", "rebound"], "article_id"=>739777, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Qualitative_changes_of_HIV_specific_CD8_T_cells_in_patients_experiencing_a_virus_rebound_following_treatment_interruption_/739777", "title"=>"Qualitative changes of HIV-specific CD8 T cells in patients experiencing a virus rebound following treatment interruption.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111483"], "description"=>"<p><b>A.</b> Functional avidity of B*0702-<sub>GPGHKARVL</sub>- and A*0301-<sub>RLRPGGKKK</sub>-specific CD8 T cells from patient #1023 before (-PTI) and after (-ATI) treatment interruption (TI) and analysis of the functional avidity of B*0702-<sub>IPRRIRQG</sub>-specific CD8 T-cell response, which was undetectable before TI. <b>B.</b> Cumulative matched-paired analysis of the functional avidity of HIV-specific CD8 T-cell responses in patients treated during acute HIV infection (PHI) before (-PTI) or after treatment interruption (-ATI) and in PHI patients after 1 (-T1Y) or 5 years (-T5Y) of uninterrupted ART. Twenty new HIV-specific CD8 T-cell responses generated ATI (New-ATI) within the same patients are also shown. <b>C.</b> Association between the fold increase in avidity of HIV-specific CD8 T-cell responses and the fold increase in the proportion of HIV-specific CD8 T cells co-expressing PD-1, 2B4 and CD160. <b>D.</b> Mixed-effect linear models were used to assess the evolution of functional avidity as a function of time and virus rebound, as detailed in the <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#s4\" target=\"_blank\">Methods</a>. Solid lines represent the lack of significant increase in avidity overtime in patient ON (red line) or OFF (green line) ART, whereas the dashed lines represent the immediate increase of functional avidity occurring after treatment interruption.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "avidity", "hiv-specific", "cd8", "cells"], "article_id"=>739781, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increase_in_functional_avidity_of_HIV_specific_CD8_T_cells_following_treatment_interruption_/739781", "title"=>"Increase in functional avidity of HIV-specific CD8 T cells following treatment interruption.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111484"], "description"=>"<p><b>A.</b> Percentage of CDR3 renewal of HIV-specific CD8 T cells before (under treatment) and after treatment interruption (TI). CDR3 diversity and renewal were determined as described <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423-Miconnet1\" target=\"_blank\">[32]</a>. Example of TRBV usage and CDR3 size pattern analysis of B*0702-<sub>GPGHKARVL</sub>-specific CD8 T cells in patient #1023 at week 18, 96 and 125 are shown in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003423#ppat.1003423.s003\" target=\"_blank\">Fig. S3</a>. <b>B.</b> Association between the percentage of CDR3 renewal and changes in the functional avidity of HIV-specific CD8 T cells.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "cdr3", "renewal", "hiv-specific", "cd8", "cells", "interruption"], "article_id"=>739782, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_CDR3_renewal_of_HIV_specific_CD8_T_cells_following_treatment_interruption_and_association_with_functional_avidity_/739782", "title"=>"Increased CDR3 renewal of HIV-specific CD8 T cells following treatment interruption and association with functional avidity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:03:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111487", "https://ndownloader.figshare.com/files/1111492", "https://ndownloader.figshare.com/files/1111499", "https://ndownloader.figshare.com/files/1111503", "https://ndownloader.figshare.com/files/1111506"], "description"=>"<div><p>The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, <i>i.e.</i> co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.</p></div>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "immunity", "Adaptive immunity", "Immunity to infections", "Immune response", "microbiology", "Virology", "Immunodeficiency viruses", "Host-pathogen interaction", "Infectious diseases", "Infectious disease control", "perturbation", "viremia", "drives", "avidity", "hiv-specific", "cd8"], "article_id"=>739785, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Selena Viganò", "Felicitas Bellutti Enders", "Isabelle Miconnet", "Cristina Cellerai", "Anne-Laure Savoye", "Virginie Rozot", "Matthieu Perreau", "Mohamed Faouzi", "Khalid Ohmiti", "Matthias Cavassini", "Pierre-Alexandre Bart", "Giuseppe Pantaleo", "Alexandre Harari"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003423.s001", "https://dx.doi.org/10.1371/journal.ppat.1003423.s002", "https://dx.doi.org/10.1371/journal.ppat.1003423.s003", "https://dx.doi.org/10.1371/journal.ppat.1003423.s004", "https://dx.doi.org/10.1371/journal.ppat.1003423.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rapid_Perturbation_in_Viremia_Levels_Drives_Increases_in_Functional_Avidity_of_HIV_specific_CD8_T_Cells_/739785", "title"=>"Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-04 02:03:24"}

PMC Usage Stats | Further Information

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Relative Metric

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