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The dual impact of HIV-1 infection and aging on naïve CD4<sup>+</sup> T-cells: Additive and distinct patterns of impairment

Rickabaugh, TM and Kilpatrick, RD and Hultin, LE and Hultin, PM and Hausner, MA and Sugar, CA and Althoff, KN and Margolick, JB and Rinaldo, CR and Detels, R and Phair, J and Effros, RB and Jamieson, BD (2011) The dual impact of HIV-1 infection and aging on naïve CD4<sup>+</sup> T-cells: Additive and distinct patterns of impairment. PLoS ONE, 6 (1).

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Abstract

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. © 2011 Rickabaugh et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rickabaugh, TM
Kilpatrick, RD
Hultin, LE
Hultin, PM
Hausner, MA
Sugar, CA
Althoff, KN
Margolick, JB
Rinaldo, CRRINALDO@pitt.eduRINALDO
Detels, R
Phair, J
Effros, RB
Jamieson, BD
Date: 7 February 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0016459
Refereed: Yes
MeSH Headings: Adult; Age Factors; Aging--immunology; Anti-Retroviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes--cytology; Case-Control Studies; HIV Infections--drug therapy; HIV Infections--immunology; Homeostasis; Humans; Longitudinal Studies; Middle Aged; T-Lymphocyte Subsets--immunology; Telomere; Thymus Gland--cytology; Young Adult
Other ID: NLM PMC3027697
PubMed Central ID: PMC3027697
PubMed ID: 21298072
Date Deposited: 03 Aug 2012 16:02
Last Modified: 13 Dec 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/13257

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