PMID- 30996090
OWN - NLM
STAT- MEDLINE
DCOM- 20200528
LR  - 20200528
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 13
DP  - 2019 Jul 1
TI  - Phenotypic and Functional Differences between Human Herpesvirus 6- and Human 
      Cytomegalovirus-Specific T Cells.
LID - 10.1128/JVI.02321-18 [doi]
LID - e02321-18
AB  - Human herpesvirus 6 (HHV-6) infects >90% of the population and establishes a 
      latent infection with asymptomatic episodes of reactivation. However, HHV-6 
      reactivation is associated with morbidity and sometimes mortality in 
      immunocompromised patients. To date, control of the virus in healthy virus 
      carriers and the failure to control it in patients with disease remain poorly 
      understood. In particular, knowledge of HHV-6-specific T-cell responses is 
      limited. Here, we characterized HHV-6A- and HHV-6B-specific CD4(+) and CD8(+) 
      T-cell responses from peripheral blood mononuclear cells (PBMCs) of healthy 
      donors. We studied the phenotype of effector HHV-6-specific T cells ex vivo, as 
      well as of induced specific suppressive regulatory CD4(+) T cells in vitro 
      poststimulation, in comparison to human cytomegalovirus (HCMV) responses. 
      Compared to that for HCMV, we show that ex vivo T-cell reactivity in peripheral 
      blood is detectable but at very low frequency, both for HHV-6A and -6B viruses. 
      Interestingly, the phenotype of the specific T cells also differs between the 
      viruses. HHV-6A- and HHV-6B-specific CD4(+) T lymphocytes are less differentiated 
      than HCMV-specific T cells. Furthermore, we show a higher frequency of 
      HHV-6-specific suppressive regulatory T cells (eTregs) than HCMV-specific eTregs 
      in coinfected individuals. Despite the strong similarity of HHV-6 and HCMV from a 
      virologic point of view, we observed immunological differences, particularly in 
      relation to the frequency and phenotype of effector/memory and regulatory 
      virus-specific T cells. This suggests that different immune factors are solicited 
      in the control of HHV-6 infection than in that of HCMV infection.IMPORTANCE T 
      cells are central to an effective defense against persistent viral infections 
      that can be related to human cytomegalovirus (HCMV) or human herpesvirus 6 
      (HHV-6). However, knowledge of HHV-6-specific T-cell responses is limited. In 
      order to deepen our knowledge of T-cell responses to HHV-6, we characterized 
      HHV-6A- and HHV-6B-specific CD4(+) and CD8(+) T-cell responses directly ex vivo 
      from healthy coinfected blood donors. Despite the strong similarity of HHV-6 and 
      HCMV from a virologic point of view, we observed immunological differences, 
      particularly in relation to the frequency and phenotype of effector/memory and 
      regulatory virus-specific T cells. This suggests that different immune factors 
      are solicited in the control of HHV-6 infection than in that of HCMV infection. 
      Our findings may encourage immunomonitoring of patients with viral replication 
      episodes to follow the emergence of effector versus regulatory T cells.
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - Fastenackels, Solene
AU  - Fastenackels S
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
FAU - Bayard, Charles
AU  - Bayard C
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
FAU - Larsen, Martin
AU  - Larsen M
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
FAU - Magnier, Philippe
AU  - Magnier P
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
FAU - Bonnafous, Pascale
AU  - Bonnafous P
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
FAU - Seddiki, Nabila
AU  - Seddiki N
AD  - INSERM U955, equipe 16, Vaccine Research Institute, Faculte de Medecine, 
      Universite Paris Est Creteil, Creteil, France.
FAU - Appay, Victor
AU  - Appay V
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France.
AD  - International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto, Japan.
FAU - Gautheret-Dejean, Agnes
AU  - Gautheret-Dejean A
AD  - APHP, Hospital Pitie-Salpetriere Paris, Laboratory of Virology, Paris, France.
FAU - Sauce, Delphine
AU  - Sauce D
AD  - INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 
      Sorbonne Universite, Paris, France delphine.sauce@upmc.fr.
LA  - eng
PT  - Journal Article
DEP - 20190614
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cytomegalovirus/*physiology
MH  - Cytomegalovirus Infections/*immunology/virology
MH  - Herpesvirus 6, Human/*physiology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Middle Aged
MH  - Paris
MH  - Phenotype
MH  - Roseolovirus Infections/*immunology/virology
MH  - T-Lymphocytes, Regulatory
MH  - Young Adult
PMC - PMC6580948
OTO - NOTNLM
OT  - HCMV
OT  - HHV-6
OT  - effector T cells
OT  - regulatory T cells
EDAT- 2019/04/19 06:00
MHDA- 2020/05/29 06:00
PMCR- 2019/12/14
CRDT- 2019/04/19 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/04/19 06:00 [pubmed]
PHST- 2020/05/29 06:00 [medline]
PHST- 2019/04/19 06:00 [entrez]
PHST- 2019/12/14 00:00 [pmc-release]
AID - JVI.02321-18 [pii]
AID - 02321-18 [pii]
AID - 10.1128/JVI.02321-18 [doi]
PST - epublish
SO  - J Virol. 2019 Jun 14;93(13):e02321-18. doi: 10.1128/JVI.02321-18. Print 2019 Jul 
      1.