title: Human immunodeficiency virus type 1-specific CD8+ T-cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells.
abstract: Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8+ T-cell responses. Here, we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific cytotoxic T-lymphocyte (CTL) responses developed during PHI in comparison to CTL responses in chronic infection and demonstrated a distinct relationship between the early virus-specific CTL responses and the viral set point, as well as the slope of CD4+ T-cell decline. CTL responses during PHI followed clear hierarchical immunodominance patterns that were lost during the transition to chronic infection. Importantly, the immunodominance patterns of human immunodeficiency virus type 1 (HIV-1)-specific CTL responses detected in primary, but not in chronic, HIV-1 infection were significantly associated with the subsequent set point of viral replication. Moreover, the preservation of the initial CD8+ T-cell immunodominance patterns from the acute into the chronic phase of infection was significantly associated with slower CD4+ T-cell decline. Taken together, these data show that the specificity of the initial CTL response to HIV is critical for the subsequent control of viremia and have important implications for the rational selection of antigens for future HIV-1 vaccines.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Jolin
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: Randall C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Chanson
authors.initials: C
authors.lastname: Brumme
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Heiko K
authors.initials: HK
authors.lastname: Jessen
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014779:Virus Replication