title: Elite controller CD8+ T cells exhibit comparable viral inhibition capacity, but better sustained effector properties compared to chronic progressors.
abstract: Mechanisms modulating HIV-specific CD8+ T cell-mediated viral inhibition are not well defined. To delineate features of effective control, we compared the ability of CD8+T cells from HIV ECs and CPs to inhibit HIV ex vivo. ECs showed superior inhibition compared to HAART-treated or untreated CPs in a typical VIA in which CD8+ T cells are rested 3 d before use (P = 0.025). In contrast, comparable antiviral activity was observed in freshly thawed cells. Rested CD8+T cells underwent apoptosis with preferential loss of HIV-specific cells. EC CD8+T cells showed greater capacity to sustain polyfunctionality ex vivo compared with those of CPs, and incubation of CD8+T cells with IL-15 augmented inhibition. These results indicate that superior ex vivo inhibition of viral replication by CD8+T cells from ECs is associated with enhanced retention of functional qualities and that in vitro antiviral function is enhanced by IL-15.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shasha
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Karel
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Angiuli
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Greenblatt
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Musie
authors.initials: M
authors.lastname: Ghebremichael
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA fporichis@mgh.harvard.edu.
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA bwalker@mgh.harvard.edu.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015925:Cryopreservation; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D006678:HIV / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014779:Virus Replication
chemical_list: D019409:Interleukin-15
keywords: HIV control; IL-15; apoptosis; polyfunctionality