Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents.
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 dif...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3139570?pdf=render |
| _version_ | 1818236676506386432 |
|---|---|
| author | Elizabeth R Sharp Christian B Willberg Peter J Kuebler Jacob Abadi Glenn J Fennelly Joanna Dobroszycki Andrew A Wiznia Michael G Rosenberg Douglas F Nixon |
| author_facet | Elizabeth R Sharp Christian B Willberg Peter J Kuebler Jacob Abadi Glenn J Fennelly Joanna Dobroszycki Andrew A Wiznia Michael G Rosenberg Douglas F Nixon |
| author_sort | Elizabeth R Sharp |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-12T12:13:39Z |
| format | Article |
| id | doaj.art-678fe0ce20704414b5075c0545e92013 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T12:13:39Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-678fe0ce20704414b5075c0545e920132022-12-22T00:24:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2113510.1371/journal.pone.0021135Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents.Elizabeth R SharpChristian B WillbergPeter J KueblerJacob AbadiGlenn J FennellyJoanna DobroszyckiAndrew A WizniaMichael G RosenbergDouglas F NixonHIV-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.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.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.http://europepmc.org/articles/PMC3139570?pdf=render |
| spellingShingle | Elizabeth R Sharp Christian B Willberg Peter J Kuebler Jacob Abadi Glenn J Fennelly Joanna Dobroszycki Andrew A Wiznia Michael G Rosenberg Douglas F Nixon Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3139570?pdf=render |
| work_keys_str_mv | AT elizabethrsharp immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT christianbwillberg immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT peterjkuebler immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT jacobabadi immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT glennjfennelly immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT joannadobroszycki immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT andrewawiznia immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT michaelgrosenberg immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents AT douglasfnixon immunodominanceofhiv1specificcd8tcellresponsesisrelatedtodiseaseprogressionrateinverticallyinfectedadolescents |