Author(s): Ribeiro, Susan Pereira ; Milush, Jeffrey M. ; Cunha-Neto, Edecio ; Kallas, Esper G. ; Kalil, Jorge ; Passero, Luiz Felipe D. [UNESP] ; Hunt, Peter W. ; Deeks, Steven G. ; Nixon, Douglas F. ; SenGupta, Devi
Date: 2018
Persistent ID: http://hdl.handle.net/11449/159204
Origin: Oasisbr
Made available in DSpace on 2018-11-26T15:37:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-11-18
Delaney AIDS Research Enterprise (DARE)
NIAID
UCSF/Gladstone Institute of Virology & Immunology CFAR
UCSF Clinical and Translational Research Institute Clinical Research Center
Center for AIDS Prevention Studies
CFAR Network of Integrated Systems
NIH NIAID
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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.
Univ Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Sao Paulo, Brazil
INCT, Iii, Sao Paulo, Brazil
Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA
Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USA
Univ Sao Paulo, Sch Med, Inst Heart, Immunol Lab, Sao Paulo, Brazil
Butantan Inst, Sao Paulo, SP, Brazil
Sao Paulo State Univ Julio de Mesquite Filho, Sao Vicent Unit, Paulista Coastal Campus, Sao Paulo, Brazil
Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, HIV AIDS Div, San Francisco, CA USA
George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA
Sao Paulo State Univ Julio de Mesquite Filho, Sao Vicent Unit, Paulista Coastal Campus, Sao Paulo, Brazil
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
FAPESP: 2010/05845-0/EGK/DFN
CNPq: 056/2012
