PMID- 32350076
OWN - NLM
STAT- MEDLINE
DCOM- 20201119
LR  - 20240427
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 94
IP  - 14
DP  - 2020 Jul 1
TI  - Delayed Expression of PD-1 and TIGIT on HIV-Specific CD8 T Cells in Untreated 
      HLA-B*57:01 Individuals Followed from Early Infection.
LID - 10.1128/JVI.02128-19 [doi]
LID - e02128-19
AB  - While the relationship of protective human leukocyte antigen (HLA) class I 
      alleles and HIV progression is well defined, the interaction of HLA-mediated 
      protection and CD8 T-cell exhaustion is less well characterized. To gain insight 
      into the influence of HLA-B*57:01 on the deterioration of CD8 T-cell responses 
      during HIV infection in the absence of antiretroviral treatment, we compared 
      HLA-B*57:01-restricted HIV-specific CD8 T-cell responses to responses restricted 
      by other HLA class I alleles longitudinally after control of peak viremia. 
      Detailed characterization of polyfunctionality, differentiation phenotypes, 
      transcription factor, and inhibitory receptor expression revealed progression of 
      CD8 T-cell exhaustion over the course of the infection in both patient groups. 
      However, early effects on the phenotype of the total CD8 T-cell population were 
      apparent only in HLA-B*57-negative patients. The HLA-B*57:01-restricted, HIV 
      epitope-specific CD8 T-cell responses showed beneficial functional patterns and 
      significantly lower frequencies of inhibitory receptor expression, i.e., PD-1 and 
      coexpression of PD-1 and TIGIT, within the first year of infection. Coexpression 
      of PD-1 and TIGIT was correlated with clinical markers of disease progression and 
      declining percentages of the T-bet(hi) Eomes(dim) CD8 T-cell population. In 
      accordance with clinical and immunological deterioration in the HLA-B*57:01 
      group, the difference in PD-1 and TIGIT receptor expression did not persist to 
      later stages of the disease.IMPORTANCE Given the synergistic nature of TIGIT and 
      PD-1, the coexpression of those inhibitory receptors should be considered when 
      evaluating T-cell pathogenesis, developing immunomodulatory therapies or vaccines 
      for HIV, and when using immunotherapy or vaccination for other causes in 
      HIV-infected patients. HIV-mediated T-cell exhaustion influences the patient s 
      disease progression, immune system and subsequently non-AIDS complications, and 
      efficacy of vaccinations against other pathogens. Consequently, the possibilities 
      of interfering with exhaustion are numerous. Expanding the use of 
      immunomodulatory therapies to include HIV treatment depends on information about 
      possible targets and their role in the deterioration of the immune system. 
      Furthermore, the rise of immunotherapies against cancer and elevated cancer 
      incidence in HIV-infected patients together increase the need for detailed 
      knowledge of T-cell exhaustion and possible interactions. A broader approach to 
      counteract immune exhaustion to alleviate complications and improve efficacy of 
      other vaccines also promises to increase patients' health and quality of life.
CI  - Copyright (c) 2020 Scharf et al.
FAU - Scharf, Lydia
AU  - Scharf L
AUID- ORCID: 0000-0002-1596-2208
AD  - Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Tauriainen, Johanna
AU  - Tauriainen J
AD  - Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Buggert, Marcus
AU  - Buggert M
AD  - Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
AD  - Department of Microbiology, University of Pennsylvania, Philadelphia, 
      Pennsylvania, USA.
FAU - Hartogensis, Wendy
AU  - Hartogensis W
AD  - Department of Medicine, University of California, San Francisco, San Francisco, 
      California, USA.
FAU - Nolan, David J
AU  - Nolan DJ
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida, Gainesville, Florida, USA.
AD  - Bioinfoexperts LLC, Alachua, Florida, USA.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - Department of Medicine, University of California, San Francisco, San Francisco, 
      California, USA.
FAU - Salemi, Marco
AU  - Salemi M
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida, Gainesville, Florida, USA.
FAU - Hecht, Frederick M
AU  - Hecht FM
AD  - Department of Medicine, University of California, San Francisco, San Francisco, 
      California, USA.
FAU - Karlsson, Annika C
AU  - Karlsson AC
AUID- ORCID: 0000-0002-2028-8393
AD  - Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden 
      annika.karlsson@ki.se.
LA  - eng
GR  - K24 AT007827/AT/NCCIH NIH HHS/United States
GR  - P01 AI071713/AI/NIAID NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200701
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (TIGIT protein, human)
SB  - IM
MH  - Adult
MH  - CD8-Positive T-Lymphocytes/*metabolism/pathology
MH  - Female
MH  - *Gene Expression Regulation
MH  - HIV Infections/*metabolism/pathology
MH  - HIV-1/*metabolism
MH  - HLA-B Antigens/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*biosynthesis
MH  - Receptors, Immunologic/*biosynthesis
PMC - PMC7343205
OTO - NOTNLM
OT  - CD4
OT  - CD8-positive T lymphocytes
OT  - HIV Gag
OT  - HIV-1
OT  - PD-1
OT  - T-cell immunoreceptor with Ig and ITIM domain
OT  - TIGIT
OT  - cellular immunity
OT  - disease progression
OT  - evolution
OT  - human HLA-B*5701 antigen
OT  - molecular evolution
OT  - programmed cell death protein 1
OT  - viral load
EDAT- 2020/05/01 06:00
MHDA- 2020/11/20 06:00
PMCR- 2020/07/01
CRDT- 2020/05/01 06:00
PHST- 2019/12/20 00:00 [received]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/05/01 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2020/05/01 06:00 [entrez]
PHST- 2020/07/01 00:00 [pmc-release]
AID - JVI.02128-19 [pii]
AID - 02128-19 [pii]
AID - 10.1128/JVI.02128-19 [doi]
PST - epublish
SO  - J Virol. 2020 Jul 1;94(14):e02128-19. doi: 10.1128/JVI.02128-19. Print 2020 Jul 
      1.