title: Susceptibility to CD8 T-cell-mediated killing influences the reservoir of latently HIV-1-infected CD4 T cells.
abstract: BACKGROUND
  HIV-1 establishes a lifelong infection in the human body, but host factors that influence viral persistence remain poorly understood. Cell-intrinsic characteristics of CD4 T cells, the main target cells for HIV-1, may affect the composition of the latent viral reservoir by altering the susceptibility to CD8 T-cell-mediated killing.
  
  
  RESULTS
  We observed that susceptibilities of CD4 T cells to CD8 T-cell-mediated killing, as determined in direct ex vivo assays, were significantly higher in persons with natural control of HIV-1 (elite controllers) than in individuals effectively treated with antiretroviral therapy. These differences were most pronounced in naive and in terminally differentiated CD4 T cells and corresponded to a reduced viral reservoir size in elite controllers. Interestingly, the highest susceptibility to CD8 T-cell-mediated killing and lowest reservoirs of cell-associated HIV-1 DNA was consistently observed in elite controllers expressing the protective HLA class I allele B57.
  
  
  CONCLUSIONS
  These data suggest that the functional responsiveness of host CD4 T cells to cytotoxic effects of HIV-1-specific CD8 T cells can contribute to shaping the structure and composition of the latently infected CD4 T-cell pool.
authors.affiliation: *Infectious Disease Division, Massachusetts General Hospital, Boston, MA; †Ragon Institute of MGH, MIT, and Harvard, Boston, MA; ‡Laboratory of AIDS Immunology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; and §Infectious Disease Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzon
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Katherine
authors.initials: K
authors.lastname: Seiss
authors.forename: Jerome
authors.initials: J
authors.lastname: Rogich
authors.forename: Sylvie
authors.initials: S
authors.lastname: Le Gall
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D020276:HIV Long-Term Survivors / Q000523:psychology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000502:physiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult