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Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents

BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesi...

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Autores principales: Sharp, Elizabeth R., Willberg, Christian B., Kuebler, Peter J., Abadi, Jacob, Fennelly, Glenn J., Dobroszycki, Joanna, Wiznia, Andrew A., Rosenberg, Michael G., Nixon, Douglas F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139570/
https://www.ncbi.nlm.nih.gov/pubmed/21818255
http://dx.doi.org/10.1371/journal.pone.0021135
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author Sharp, Elizabeth R.
Willberg, Christian B.
Kuebler, Peter J.
Abadi, Jacob
Fennelly, Glenn J.
Dobroszycki, Joanna
Wiznia, Andrew A.
Rosenberg, Michael G.
Nixon, Douglas F.
author_facet Sharp, Elizabeth R.
Willberg, Christian B.
Kuebler, Peter J.
Abadi, Jacob
Fennelly, Glenn J.
Dobroszycki, Joanna
Wiznia, Andrew A.
Rosenberg, Michael G.
Nixon, Douglas F.
author_sort Sharp, Elizabeth R.
collection PubMed
description BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.
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spelling pubmed-31395702011-08-04 Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents Sharp, Elizabeth R. Willberg, Christian B. Kuebler, Peter J. Abadi, Jacob Fennelly, Glenn J. Dobroszycki, Joanna Wiznia, Andrew A. Rosenberg, Michael G. Nixon, Douglas F. PLoS One Research Article BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions. Public Library of Science 2011-07-19 /pmc/articles/PMC3139570/ /pubmed/21818255 http://dx.doi.org/10.1371/journal.pone.0021135 Text en Sharp et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sharp, Elizabeth R.
Willberg, Christian B.
Kuebler, Peter J.
Abadi, Jacob
Fennelly, Glenn J.
Dobroszycki, Joanna
Wiznia, Andrew A.
Rosenberg, Michael G.
Nixon, Douglas F.
Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title_full Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title_fullStr Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title_full_unstemmed Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title_short Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
title_sort immunodominance of hiv-1 specific cd8+ t-cell responses is related to disease progression rate in vertically infected adolescents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139570/
https://www.ncbi.nlm.nih.gov/pubmed/21818255
http://dx.doi.org/10.1371/journal.pone.0021135
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