title: Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection.
abstract: Attrition within the CD4(+)T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8(+)T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8(+)T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38(+)CD27(-)CD8(+)T cells characterized by the low expression of the CD8 receptor (CD8(dim)). Interestingly, while high frequencies of HIV-specific CD8(+)T cell responses occur within the CD38(+)CD27(-)CD8(dim)T cell population, the minority populations of CD8(bright)T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8(dim)T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8(dim)T cells, and the size of this population inversely correlates with the acute loss of CD4(+)T cells. These data indicate, for the first time, that early CD4(+)T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8(dim)T cell population less efficient in controlling HIV viremia.
  
  
  OBJECTIVE
  A distinct population of activated CD8(+)T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8(+)T cell dysfunction during acute infection.
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Michael A
authors: MA
authors: Eller
authors: Department of Immunology & Microbiology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Nilu
authors: N
authors: Goonetilleke
authors: Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Boonrat
authors: B
authors: Tassaneetrithep
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Leigh Anne
authors: LA
authors: Eller
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Margaret C
authors: MC
authors: Costanzo
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Susan
authors: S
authors: Johnson
authors: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Michael R
authors: MR
authors: Betts
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Shelly J
authors: SJ
authors: Krebs
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Bonnie M
authors: BM
authors: Slike
authors: Department of Retrovirology, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors: Sorachai
authors: S
authors: Nitayaphan
authors: Walter Reed Project-Kenya, Kericho, Kenya.
authors: Kathleen
authors: K
authors: Rono
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Sodsai
authors: S
authors: Tovanabutra
authors: Walter Reed Program-Tanzania, Mbeya, Tanzania.
authors: Lucas
authors: L
authors: Maganga
authors: Makerere University Walter Reed Project, Kampala, Uganda.
authors: Hannah
authors: H
authors: Kibuuka
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors: Linda
authors: L
authors: Jagodzinski
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors: Sheila
authors: S
authors: Peel
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Morgane
authors: M
authors: Rolland
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors: Mary A
authors: MA
authors: Marovich
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|International Vaccine Institute, Seoul, South Korea.
authors: Jerome H
authors: JH
authors: Kim
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors: Nelson L
authors: NL
authors: Michael
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors: Merlin L
authors: ML
authors: Robb
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA Hendrik.streeck@uk-essen.de.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.|Institute for HIV Research, University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
authors: Hendrik
authors: H
authors: Streeck
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D000939:Epitopes; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000939:Epitopes