PMID- 25660021
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220131
IS  - 2211-1247 (Electronic)
VI  - 10
IP  - 5
DP  - 2015 Feb 10
TI  - Immunomodulation of Selective Naive T Cell Functions by p110delta Inactivation 
      Improves the Outcome of Mismatched Cell Transplantation.
PG  - 702-710
LID - S2211-1247(15)00003-0 [pii]
LID - 10.1016/j.celrep.2015.01.002 [doi]
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) can treat certain 
      hematologic malignancies due to the graft versus leukemia (GvL) effect but is 
      complicated by graft versus host disease (GvHD). Expression of the p110delta 
      catalytic subunit of the phosphoinositide 3-kinase pathway is restricted to 
      leukocytes, where it regulates proliferation, migration, and cytokine production. 
      Here, in a mouse model of fully mismatched hematopoietic cell transplantation 
      (HCT), we show that genetic inactivation of p110delta in T cells leads to milder 
      GvHD, whereas GvL is preserved. Inactivation of p110delta in human lymphocytes 
      reduced T cell allorecognition. We demonstrate that both allostimulation and 
      granzyme B expression were dependent on p110delta in naive T cells, which are the 
      main mediators of GvHD, whereas memory T cells were unaffected. Strikingly, p110delta 
      is not mandatory for either naive or memory T cells to mediate GvL. Therefore, 
      immunomodulation of selective naive T cell functions by p110delta inactivation 
      improves the outcome of allogeneic HSCT.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Doisne, Jean-Marc
AU  - Doisne JM
AD  - Department of Obstetrics and Gynaecology, University of Cambridge School of 
      Clinical Medicine, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0SW, 
      UK. Electronic address: jmd83@medschl.cam.ac.uk.
FAU - Huber, Christian M
AU  - Huber CM
AD  - Department of Obstetrics and Gynaecology, University of Cambridge School of 
      Clinical Medicine, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0SW, 
      UK.
FAU - Okkenhaug, Klaus
AU  - Okkenhaug K
AD  - Laboratory for Lymphocyte Signaling and Development, Babraham Research Campus, 
      The Babraham Institute, Cambridge CB22 3AT, UK.
FAU - Colucci, Francesco
AU  - Colucci F
AD  - Department of Obstetrics and Gynaecology, University of Cambridge School of 
      Clinical Medicine, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0SW, 
      UK.
LA  - eng
GR  - 095691/WT_/Wellcome Trust/United Kingdom
GR  - BBS/E/B/000C0409/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
PT  - Journal Article
DEP - 20150205
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
PMC - PMC4542309
EDAT- 2015/02/11 06:00
MHDA- 2015/02/11 06:01
PMCR- 2015/02/05
CRDT- 2015/02/10 06:00
PHST- 2014/06/02 00:00 [received]
PHST- 2014/11/11 00:00 [revised]
PHST- 2014/12/24 00:00 [accepted]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2015/02/11 06:01 [medline]
PHST- 2015/02/10 06:00 [entrez]
PHST- 2015/02/05 00:00 [pmc-release]
AID - S2211-1247(15)00003-0 [pii]
AID - 10.1016/j.celrep.2015.01.002 [doi]
PST - ppublish
SO  - Cell Rep. 2015 Feb 10;10(5):702-710. doi: 10.1016/j.celrep.2015.01.002. Epub 2015 
      Feb 5.