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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Published in:PloS one Vol. 6; no. 1; p. e16459
Main Authors: 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.
Format: Journal Article
Language:English
Published: United States Public Library of Science 26.01.2011
Public Library of Science (PLoS)
Subjects:
Acquired immune deficiency syndrome
Adult
Adults
Age
Age Factors
Aging
Aging - immunology
AIDS
Anti-Retroviral Agents
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Biology
Case-Control Studies
CD4 antigen
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - cytology
CD45RA antigen
Cytokines
Cytotoxicity
Drug therapy
Emigration
Epidemiology
Frailty
Hemophilia
HIV
HIV Infections - drug therapy
HIV Infections - immunology
Homeostasis
Human immunodeficiency virus
Humans
Immune response
Immunology
Infections
Inflammation
Liver
Liver diseases
Longitudinal Studies
Lymphocytes T
Lymphoma
Medicine
Middle Aged
Morbidity
Neoantigens
Older people
Public health
Signal transduction
T-Lymphocyte Subsets - immunology
Telomerase
Telomere
Thymus
Thymus Gland - cytology
Trends
Young Adult
Los Angeles California
California
United States > US
Maryland
Baltimore Maryland
ISSN:1932-6203, 1932-6203
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Summary: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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Conceived and designed the experiments: TMR RDK BDJ. Performed the experiments: TMR LEH PMH MAH. Analyzed the data: CAS RDK. Contributed reagents/materials/analysis tools: JBM CRR RD JP KNA. Wrote the paper: TMR BDJ. Provided intellectual contribution, assisted in data interpretation: RBE.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0016459