p16(INK4a) Expression and Immunologic Aging in Chronic HIV Infection

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author RIBEIRO, Susan Pereira FMUSP-HC
MILUSH, Jeffrey M.
PASSERO, Luiz Felipe D.
HUNT, Peter W.
DEEKS, Steven G.
NIXON, Douglas F.
dc.date.issued 2016
dc.identifier.citation PLOS ONE, v.11, n.11, article ID e0166759, 9p, 2016
dc.identifier.issn 1932-6203
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/17802
dc.description.abstract Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16(INK4a) (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited increased per-cell p16 protein expression that was discordant with chronological aging. ART restored p16 protein expression to levels comparable with HIV-negative subjects in the CD4 compartment, but not in CD8 T cells, which can be an indicative of an irreversible activation/exhaustion status on these cells. Additionally, the frequency of activated CD4+ and CD8+ T cells was positively correlated with p16 expression in CD4+ and CD8+ T cells in untreated subjects. In contrast to healthy controls, untreated HIV-infected individuals had increased p16 levels within the effector memory (T-EM) subset, indicating a possible role for this marker in impaired clonal expansion during antiviral effector function. Taken together, these data demonstrate that chronic HIV infection is associated with elevated expression of the cellular aging marker p16 in T cells. ART restored normal p16 levels in the CD4+ T cell compartment, indicating that use of therapy can be of fundamental importance to normal cell cycling and maintaining immune homeostasis.
dc.description.sponsorship · Delaney AIDS Research Enterprise (DARE) [AI096109]
· NIAID [K24 AI069994]
· UCSF/Gladstone Institute of Virology & Immunology CFAR [P30 AI027763]
· UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]
· Center for AIDS Prevention Studies [P30 MH62246]
· CFAR Network of Integrated Systems [R24 AI067039]
· NIH NIAID [K08 A120071]
· Brazilian Council for Scientific and Technological Development (CNPq)
· Sao Paulo State Research Funding Agency (FAPESP)
· Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2010/05845-0/EGK/DFN]
· CNPq/CAPES [056/2012]
dc.language.iso eng
dc.relation.ispartof Plos One
dc.rights openAccess
dc.subject.other immunosenescence; mechanisms; senescence
dc.title p16(INK4a) Expression and Immunologic Aging in Chronic HIV Infection
dc.type article
dc.rights.holder Copyright PUBLIC LIBRARY SCIENCE
dc.description.group LIM/60
dc.description.group LIM/19
dc.identifier.doi 10.1371/journal.pone.0166759
dc.identifier.pmid 27861555
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author RIBEIRO, Susan Pereira:HC:LIM/60
hcfmusp.author CUNHA-NETO, Edecio:FM:MCM
hcfmusp.author KALLAS, Esper G.:FM:MCM
hcfmusp.author KALIL, Jorge:FM:MCM
hcfmusp.author.external · MILUSH, Jeffrey M.:Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USA
· PASSERO, Luiz Felipe D.:Sao Paulo State Univ Julio de Mesquite Filho, Sao Vicent Unit, Paulista Coastal Campus, Sao Paulo, Brazil
· HUNT, Peter W.:Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, HIV AIDS Div, San Francisco, CA USA
· DEEKS, Steven G.:Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, HIV AIDS Div, San Francisco, CA USA
· NIXON, Douglas F.:George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA
· SENGUPTA, Devi:Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USA
hcfmusp.origem.id 2-s2.0-84995910843
hcfmusp.origem.id WOS:000388350300102
hcfmusp.publisher.city SAN FRANCISCO
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
hcfmusp.citation.scopus 2
hcfmusp.citation.wos 3
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Estados Unidos

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