PMID- 26731751
OWN - NLM
STAT- MEDLINE
DCOM- 20161114
LR  - 20161230
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 30
IP  - 1
DP  - 2016 Jan 2
TI  - The presence of protective cytotoxic T lymphocytes does not correlate with 
      shorter lifespans of productively infected cells in HIV-1 infection.
PG  - 9-17
LID - 10.1097/QAD.0000000000000914 [doi]
AB  - OBJECTIVES AND DESIGN: CD8+ cytotoxic T lymphocytes (CTL) are important in the 
      control of HIV infection. Although CTL are thought to reduce the lifespan of 
      productively infected cells, CD8+ T-cell depletion in simian immunodeficiency 
      virus-infected rhesus-macaques showed no effect on the lifespan of productively 
      infected cells. As CD8+ T-cell responses that successfully delay HIV disease 
      progression occur only in a minority of HIV-infected individuals, we studied the 
      hypothesis that the ability of CTL to reduce the lifespan of productively 
      infected cells is limited to protective CTL responses only. METHODS: We 
      correlated features of CD8+ T cells that are associated with control of HIV 
      infection, namely restriction by protective human leukocyte antigen (HLA) 
      alleles, and/or a broad, high or poly-functional Gag-specific CD8+ T-cell 
      response, to the lifespan of productively infected cells in 36 HIV-infected 
      individuals, by measuring their plasma viral load declines immediately after 
      start of combined antiretroviral therapy. RESULTS: The average lifespan of 
      productively HIV-infected cells varied greatly between individuals, from 1.01 to 
      3.68 days (median 1.82 days) but was not different between individuals with or 
      without the protective HLA molecules B27 or B57 (P=0.76, median 1.94 and 1.79 
      days, respectively). Although the CD8+ T-cell response against HIV Gag was the 
      dominant HIV-specific T-cell response, its magnitude (r=0.02, P = 0.5), breadth 
      (r = 0.03, P = 0.4), and poly-functionality (r = 0.01, P = 0.8), did not 
      correlate with the lifespan of productively HIV-infected cells. CONCLUSION: The 
      features of CD8+ T-cell responses that have clearly been associated with control 
      of HIV infection do not correlate with a reduced lifespan of productively 
      infected cells in vivo. This suggests that protective CD8+ T cells exert their 
      effect on target-cells before onset of productive infection, or via noncytolytic 
      mechanisms.
FAU - Spits, Hilde B
AU  - Spits HB
AD  - aLaboratory of Translational ImmunologybDepartment of Internal Medicine and 
      Infectious Diseases, University Medical Center Utrecht, UtrechtcDepartment of 
      Immune Mechanisms, National Institute for Public Health and the Environment 
      (RIVM), BilthovendDepartment of Medical Microbiology, Virology, University 
      Medical Center Utrecht, UtrechteDepartment of Internal Medicine, Division of 
      Infectious Diseases, Academic Medical Center, Amsterdam, the Netherlands.
FAU - Mudrikova, Tania
AU  - Mudrikova T
FAU - Schellens, Ingrid M M
AU  - Schellens IM
FAU - Wensing, Annemarie M J
AU  - Wensing AM
FAU - Prins, Jan M
AU  - Prins JM
FAU - Feuth, Thijs
AU  - Feuth T
FAU - Spierings, Erik
AU  - Spierings E
FAU - Nijhuis, Monique
AU  - Nijhuis M
FAU - van Baarle, Debbie
AU  - van Baarle D
FAU - Borghans, Jose A M
AU  - Borghans JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-Retroviral Agents)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Anti-Retroviral Agents/therapeutic use
MH  - Female
MH  - HIV Infections/drug therapy/*immunology
MH  - HIV-1/*immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Viral Load
EDAT- 2016/01/06 06:00
MHDA- 2016/11/15 06:00
CRDT- 2016/01/06 06:00
PHST- 2016/01/06 06:00 [entrez]
PHST- 2016/01/06 06:00 [pubmed]
PHST- 2016/11/15 06:00 [medline]
AID - 00002030-201601020-00002 [pii]
AID - 10.1097/QAD.0000000000000914 [doi]
PST - ppublish
SO  - AIDS. 2016 Jan 2;30(1):9-17. doi: 10.1097/QAD.0000000000000914.