title: The dual impact of HIV-1 infection and aging on naïve CD4 T-cells: additive and distinct patterns of impairment.
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.
authors.affiliation: Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Rickabaugh
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Kilpatrick
authors.forename: Lance E
authors.initials: LE
authors.lastname: Hultin
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hultin
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hausner
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sugar
authors.forename: Keri N
authors.initials: KN
authors.lastname: Althoff
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Rita B
authors.initials: RB
authors.lastname: Effros
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D044966:Anti-Retroviral Agents; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016022:Case-Control Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016615:Telomere; D013950:Thymus Gland / Q000166:cytology; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents