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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Vydáno v:	PloS one Ročník 6; číslo 1; s. e16459
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 26.01.2011 Public Library of Science (PLoS)
Témata:	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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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