PMID- 28397358
OWN - NLM
STAT- MEDLINE
DCOM- 20180216
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 17
IP  - 8
DP  - 2017 Aug
TI  - Depletion-Resistant CD4 T Cells Enhance Thymopoiesis During Lymphopenia.
PG  - 2008-2019
LID - 10.1111/ajt.14309 [doi]
AB  - Lymphoablation is routinely used in transplantation, and its success is defined 
      by the balance of pathogenic versus protective T cells within reconstituted 
      repertoire. While homeostatic proliferation and thymopoiesis may both cause T 
      cell recovery during lymphopenia, the relative contributions of these mechanisms 
      remain unclear. The goal of this study was to investigate the role of the thymus 
      during T cell reconstitution in adult allograft recipients subjected to 
      lymphoablative induction therapy. Compared with euthymic mice, thymectomized 
      heart allograft recipients demonstrated severely impaired CD4 and CD8 T cell 
      recovery and prolonged heart allograft survival after lymphoablation with murine 
      anti-thymocyte globulin (mATG). The injection with agonistic anti-CD40 mAb or 
      thymus transplantation only partially restored T cell reconstitution in 
      mATG-treated thymectomized mice. After mATG depletion, residual CD4 T cells 
      migrated into the thymus and enhanced thymopoiesis. Conversely, depletion of CD4 
      T cells before lymphoablation inhibited thymopoiesis at the stage of CD4(-) 
      CD8(-) CD44(hi) CD25(+) immature thymocytes. This is the first demonstration that 
      the thymus and peripheral CD4 T cells cooperate to ensure optimal T cell 
      reconstitution after lymphoablation. Targeting thymopoiesis through manipulating 
      functions of depletion-resistant helper T cells may thus improve therapeutic 
      benefits and minimize the risks of lymphoablation in clinical settings.
CI  - (c) 2017 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Ayasoufi, K
AU  - Ayasoufi K
AD  - Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, 
      OH.
AD  - Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of 
      Case Western Reserve University, Cleveland, OH.
FAU - Fan, R
AU  - Fan R
AD  - Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, 
      OH.
FAU - Valujskikh, A
AU  - Valujskikh A
AD  - Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, 
      OH.
LA  - eng
GR  - R01 AI113142/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170517
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
SB  - IM
CIN - Am J Transplant. 2017 Aug;17(8):1970-1971. PMID: 28544604
MH  - Animals
MH  - Female
MH  - *Heart Transplantation
MH  - *Immunologic Memory
MH  - *Lymphocyte Depletion
MH  - Lymphopenia/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Thymus Gland/*cytology/immunology/*transplantation
PMC - PMC5519419
MID - NIHMS866984
OTO - NOTNLM
OT  - Immunosuppressant
OT  - T cell biology
OT  - basic (laboratory) research/science
OT  - immunobiology
OT  - immunosuppression/immune modulation
OT  - immunosuppressive regimens
OT  - induction
OT  - lymphocyte biology
OT  - polyclonal preparations: rabbit anti-thymocyte globulin
OT  - thymus/thymic biology
COIS- Disclosure The authors of this manuscript have no conflicts of interest to 
      disclose as described by the American Journal of Transplantation.
EDAT- 2017/04/12 06:00
MHDA- 2018/02/17 06:00
PMCR- 2018/08/01
CRDT- 2017/04/12 06:00
PHST- 2017/01/13 00:00 [received]
PHST- 2017/03/08 00:00 [revised]
PHST- 2017/04/01 00:00 [accepted]
PHST- 2017/04/12 06:00 [pubmed]
PHST- 2018/02/17 06:00 [medline]
PHST- 2017/04/12 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - S1600-6135(22)25085-0 [pii]
AID - 10.1111/ajt.14309 [doi]
PST - ppublish
SO  - Am J Transplant. 2017 Aug;17(8):2008-2019. doi: 10.1111/ajt.14309. Epub 2017 May 
      17.