PMID- 29387134
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 1742-4933 (Print)
IS  - 1742-4933 (Electronic)
IS  - 1742-4933 (Linking)
VI  - 15
DP  - 2018
TI  - Molecular changes associated with increased TNF-alpha-induced apoptotis in naive 
      (T(N)) and central memory (T(CM)) CD8+ T cells in aged humans.
PG  - 2
LID - 10.1186/s12979-017-0109-0 [doi]
LID - 2
AB  - BACKGROUND: Progressive T cell decline in aged humans is associated with a 
      deficiency of naive (T(N)) and central memory (T(CM)) T cells. We have previously 
      reported increased Tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in T(N) and 
      T(CM) T cells in aged humans; however, the molecular basis of increased apoptosis 
      remains to be defined. Since expression of TNF receptors (TNFRs) was reported to 
      be comparable in young and aged, we investigated signaling events downstream of 
      TNFRs to understand the molecular basis of increased TNF-alpha-induced apoptosis in 
      aged T(N) and T(CM) CD8+ cells. RESULTS: The expression of TRAF-2 and RIP, 
      phosphorylation of JNK, IKKalpha/beta, and IkappaBalpha, and activation of NF-kappaB activation were 
      significantly decreased in T(N) and T(CM) CD8+ cells from aged subjects as 
      compared to young controls. Furthermore, expression of A20, Bcl-x(L), cIAP1, and 
      FLIP-(L) and FLIP-(S) was significantly decreased in T(N) and T(CM) CD8+ cells 
      from aged subjects. CONCLUSIONS: These data demonstrate that an impaired 
      expression/function of molecules downstream TNFR signaling pathway that confer 
      survival signals contribute to increased apoptosis of T(N) and T(CM) CD8+ cells 
      in aged humans.
FAU - Gupta, Sudhir
AU  - Gupta S
AD  - 1Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical 
      Immunology, University of California, Irvine, USA. ISNI: 0000 0001 0668 7243. 
      GRID: grid.266093.8
AD  - 2Division of Basic and Clinical Immunology, Medical Sci. I, C-240, University of 
      California at Irvine, Irvine, CA 92697 USA. ISNI: 0000 0001 0668 7243. GRID: 
      grid.266093.8
FAU - Su, Houfen
AU  - Su H
AD  - 1Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical 
      Immunology, University of California, Irvine, USA. ISNI: 0000 0001 0668 7243. 
      GRID: grid.266093.8
FAU - Agrawal, Sudhanshu
AU  - Agrawal S
AD  - 1Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical 
      Immunology, University of California, Irvine, USA. ISNI: 0000 0001 0668 7243. 
      GRID: grid.266093.8
FAU - Gollapudi, Sastry
AU  - Gollapudi S
AD  - 1Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical 
      Immunology, University of California, Irvine, USA. ISNI: 0000 0001 0668 7243. 
      GRID: grid.266093.8
LA  - eng
PT  - Journal Article
DEP - 20180119
PL  - England
TA  - Immun Ageing
JT  - Immunity & ageing : I & A
JID - 101235427
PMC - PMC5775550
OTO - NOTNLM
OT  - A20
OT  - NF-kappab
OT  - RIP
OT  - TNF-alpha
OT  - TRAF-2
OT  - cFLIP
COIS- The study was carried out in accordance with the recommendation of The 
      Institution Review Board Committee (Human) of the University of California, 
      Irvine with approved protocol and informed consent from all subjects. All 
      subjects gave informed consent according to the Declaration of Helsinki. The 
      protocol and consent forms were approved by Institutional Review Board Human 
      Subject Committee.Approved and signed consent form lists consent to publish.The 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.Springer Nature remains neutral with regard to jurisdictional claims in 
      published maps and institutional affiliations.
EDAT- 2018/02/02 06:00
MHDA- 2018/02/02 06:01
PMCR- 2018/01/19
CRDT- 2018/02/02 06:00
PHST- 2017/10/08 00:00 [received]
PHST- 2017/12/28 00:00 [accepted]
PHST- 2018/02/02 06:00 [entrez]
PHST- 2018/02/02 06:00 [pubmed]
PHST- 2018/02/02 06:01 [medline]
PHST- 2018/01/19 00:00 [pmc-release]
AID - 109 [pii]
AID - 10.1186/s12979-017-0109-0 [doi]
PST - epublish
SO  - Immun Ageing. 2018 Jan 19;15:2. doi: 10.1186/s12979-017-0109-0. eCollection 2018.