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The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment

HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in olde...

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Autores principales: Rickabaugh, Tammy M., Kilpatrick, Ryan D., Hultin, Lance E., Hultin, Patricia M., Hausner, Mary Ann, Sugar, Catherine A., Althoff, Keri N., Margolick, Joseph B., Rinaldo, Charles R., Detels, Roger, Phair, John, Effros, Rita B., Jamieson, Beth D.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027697/
https://www.ncbi.nlm.nih.gov/pubmed/21298072
http://dx.doi.org/10.1371/journal.pone.0016459
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author Rickabaugh, Tammy M.
Kilpatrick, Ryan D.
Hultin, Lance E.
Hultin, Patricia M.
Hausner, Mary Ann
Sugar, Catherine A.
Althoff, Keri N.
Margolick, Joseph B.
Rinaldo, Charles R.
Detels, Roger
Phair, John
Effros, Rita B.
Jamieson, Beth D.
author_facet Rickabaugh, Tammy M.
Kilpatrick, Ryan D.
Hultin, Lance E.
Hultin, Patricia M.
Hausner, Mary Ann
Sugar, Catherine A.
Althoff, Keri N.
Margolick, Joseph B.
Rinaldo, Charles R.
Detels, Roger
Phair, John
Effros, Rita B.
Jamieson, Beth D.
author_sort Rickabaugh, Tammy M.
collection PubMed
description HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA(+)CD31(+) and CD45RA(+)CD31(-)) within the naïve CD4(+) T-cell compartment in young (20–32 years old) and older (39–58 years old), ART-naïve, HIV-1 seropositive individuals within 1–3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA(+)CD31(+)CD4(+) and CD45RA(+)CD31(-)CD4(+) T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA(+)CD31(+)CD4(+) T-cells two years post-ART, but minimal reconstitution of the CD45RA(+)CD31(-)CD4(+) subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4(+) T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults.
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spelling pubmed-30276972011-02-04 The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment Rickabaugh, Tammy M. Kilpatrick, Ryan D. Hultin, Lance E. Hultin, Patricia M. Hausner, Mary Ann Sugar, Catherine A. Althoff, Keri N. Margolick, Joseph B. Rinaldo, Charles R. Detels, Roger Phair, John Effros, Rita B. Jamieson, Beth D. PLoS One Research Article HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA(+)CD31(+) and CD45RA(+)CD31(-)) within the naïve CD4(+) T-cell compartment in young (20–32 years old) and older (39–58 years old), ART-naïve, HIV-1 seropositive individuals within 1–3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA(+)CD31(+)CD4(+) and CD45RA(+)CD31(-)CD4(+) T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA(+)CD31(+)CD4(+) T-cells two years post-ART, but minimal reconstitution of the CD45RA(+)CD31(-)CD4(+) subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4(+) T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults. Public Library of Science 2011-01-26 /pmc/articles/PMC3027697/ /pubmed/21298072 http://dx.doi.org/10.1371/journal.pone.0016459 Text en Rickabaugh 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
Rickabaugh, Tammy M.
Kilpatrick, Ryan D.
Hultin, Lance E.
Hultin, Patricia M.
Hausner, Mary Ann
Sugar, Catherine A.
Althoff, Keri N.
Margolick, Joseph B.
Rinaldo, Charles R.
Detels, Roger
Phair, John
Effros, Rita B.
Jamieson, Beth D.
The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title_full The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title_fullStr The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title_full_unstemmed The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title_short The Dual Impact of HIV-1 Infection and Aging on Naïve CD4(+) T-Cells: Additive and Distinct Patterns of Impairment
title_sort dual impact of hiv-1 infection and aging on naïve cd4(+) t-cells: additive and distinct patterns of impairment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027697/
https://www.ncbi.nlm.nih.gov/pubmed/21298072
http://dx.doi.org/10.1371/journal.pone.0016459
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