PMID- 21048108
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20211203
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 11
DP  - 2010 Dec 1
TI  - The Pim kinase pathway contributes to survival signaling in primed CD8+ T cells 
      upon CD27 costimulation.
PG  - 6670-8
LID - 10.4049/jimmunol.1000159 [doi]
AB  - Stimulation of the costimulatory receptor CD27 by its ligand CD70 has proved 
      important for the generation of primary and memory CD8(+) T cell responses in 
      various models of antigenic challenge. CD27/CD70-mediated costimulation promotes 
      the survival of primed T cells and thereby increases the size of effector and 
      memory populations. In this paper, we reveal molecular mechanisms underlying the 
      prosurvival effect of CD27. CD27 signaling upregulated expression of the 
      antiapoptotic Bcl-2 family member Bcl-x(L). However, genetic reconstitution of 
      Cd27(-/-) CD8(+) T cells with Bcl-x(L) alone or in combination with the related 
      protein Mcl-1 did not compensate for CD27 deficiency in the response to influenza 
      virus infection. This suggested that CD27 supports generation of the CD8(+) 
      effector T cell pool not only by counteracting apoptosis via Bcl-2 family 
      members. Genome-wide mRNA expression profiling indicated that CD27 directs 
      expression of the Pim1 gene. Pim-1 is a serine/threonine kinase that sustains 
      survival of rapidly proliferating cells by antiapoptotic and prometabolic effects 
      that are independent of the mammalian target of rapamycin (mTOR) pathway. In 
      TCR-primed CD8(+) T cells, CD27 could increment Pim-1 protein expression and 
      promote cell survival throughout clonal expansion independent of the mTOR and 
      IL-2R pathways. In addition, introduction of the Pim1 gene in Cd27(-/-) CD8(+) T 
      cells partially corrected their defect in clonal expansion and formation of an 
      effector pool. We conclude that CD27 may contribute to the survival of primed 
      CD8(+) T cells by the upregulation of antiapoptotic Bcl-2 family members but also 
      calls the Pim-1 kinase survival pathway into action.
FAU - Peperzak, Victor
AU  - Peperzak V
AD  - Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - Veraar, Elise A M
AU  - Veraar EA
FAU - Keller, Anna M
AU  - Keller AM
FAU - Xiao, Yanling
AU  - Xiao Y
FAU - Borst, Jannie
AU  - Borst J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101103
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (proto-oncogene proteins pim)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins/biosynthesis/genetics
MH  - CD8-Positive T-Lymphocytes/enzymology/*immunology/*metabolism
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cell Survival/immunology
MH  - Clone Cells
MH  - Influenza A virus/immunology
MH  - Lymphocyte Activation/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Proto-Oncogene Proteins c-pim-1/*physiology
MH  - Signal Transduction/genetics/*immunology
MH  - TOR Serine-Threonine Kinases/metabolism/physiology
MH  - Tumor Necrosis Factor Receptor Superfamily, Member 
      7/deficiency/genetics/*physiology
MH  - bcl-X Protein/biosynthesis/genetics
EDAT- 2010/11/05 06:00
MHDA- 2011/01/11 06:00
CRDT- 2010/11/05 06:00
PHST- 2010/11/05 06:00 [entrez]
PHST- 2010/11/05 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
AID - jimmunol.1000159 [pii]
AID - 10.4049/jimmunol.1000159 [doi]
PST - ppublish
SO  - J Immunol. 2010 Dec 1;185(11):6670-8. doi: 10.4049/jimmunol.1000159. Epub 2010 
      Nov 3.