PMID- 36186130
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221004
IS  - 2152-5250 (Print)
IS  - 2152-5250 (Electronic)
IS  - 2152-5250 (Linking)
VI  - 13
IP  - 5
DP  - 2022 Oct 1
TI  - Absence of TSC1 Accelerates CD8(+) T cell-mediated Acute Cardiac Allograft 
      Rejection.
PG  - 1562-1575
LID - 10.14336/AD.2022.0224 [doi]
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by 
      inactivating mutations in TSC1 or TSC2.Patients with TSC often require organ 
      transplantation after organ failure. TSC1 serves as an important control node in 
      immune cell development and responses; however, its effect on T cells in 
      transplant immunity has not yet been explored. Here, we characterized the effect 
      of TSC1 deficiency in T cells on acute allograft rejection using a mouse cardiac 
      transplantation model. We observed compromised allograft survival in mice with 
      TSC1-deficient T cells. Notably, the allografts in mice transferred with 
      TSC1-deficient CD8(+)T cells showed accelerated acute allograft rejection. TSC1 
      deficiency triggered the increased accumulation of CD8(+) T cells in allografts 
      due to augmented infiltration caused by increased CXCR3 expression levels and 
      elevated in-situ proliferation of TSC1-deficient CD8(+) T cells. Compared to 
      CD8(+) T cells from wild-type (WT) mice, TSC1-deficient CD8(+) T cells exhibited 
      enhanced cell proliferation and increased expression levels of interferon-gamma and 
      granzyme B after alloantigen stimulation. Rapamycin, an inhibitor of mammalian 
      target of rapamycin (mTOR), is used to treat patients with TSC and prevent 
      rejection after solid-organ transplantation. Although rapamycin induced most 
      cardiac allografts to survive beyond 100 d in WT mice, rapamycin-treated cardiac 
      allografts in TSC1-deficient mice were rejected within 60 d. These results 
      suggest that TSC1-deficient recipients may be more resistant to 
      rapamycin-mediated immunosuppression during organ transplantation. Collectively, 
      TSC1 significantly accelerates acute allograft rejection by enhancing the 
      alloreactivity of CD8(+) T cells, making them more resistant to mTOR 
      inhibitor-mediated immunosuppression.
CI  - copyright: (c) 2022 Tan et al.
FAU - Tan, Liang
AU  - Tan L
AD  - 1Department of Kidney Transplantation, Second Xiangya Hospital of Central South 
      University, Changsha, China.
AD  - 2Clinical Research Center for Organ Transplantation in Hunan Province, Changsha, 
      China.
FAU - Xu, Yanan
AU  - Xu Y
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FAU - Lan, Gongbin
AU  - Lan G
AD  - 1Department of Kidney Transplantation, Second Xiangya Hospital of Central South 
      University, Changsha, China.
AD  - 2Clinical Research Center for Organ Transplantation in Hunan Province, Changsha, 
      China.
FAU - Wang, Hongxia
AU  - Wang H
AD  - 4Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong, China.
FAU - Liang, Zhanfeng
AU  - Liang Z
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhang, Zhaoqi
AU  - Zhang Z
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FAU - Tian, Qianchuan
AU  - Tian Q
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FAU - Hou, Yangxiao
AU  - Hou Y
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhao, Yong
AU  - Zhao Y
AD  - 3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy 
      of Sciences, University of Chinese Academy of Sciences, Beijing, China.
AD  - 5Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 
      China.
FAU - Xie, Xubiao
AU  - Xie X
AD  - 1Department of Kidney Transplantation, Second Xiangya Hospital of Central South 
      University, Changsha, China.
AD  - 2Clinical Research Center for Organ Transplantation in Hunan Province, Changsha, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20221001
PL  - United States
TA  - Aging Dis
JT  - Aging and disease
JID - 101540533
PMC - PMC9466980
OTO - NOTNLM
OT  - acute rejection
OT  - cardiac transplantation
OT  - tuberous sclerosis complex 1
COIS- Conflicts of interest All authors have no conflict of interest to declare.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/04 06:01
PMCR- 2022/10/01
CRDT- 2022/10/03 04:29
PHST- 2021/12/18 00:00 [received]
PHST- 2022/02/24 00:00 [accepted]
PHST- 2022/10/03 04:29 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/04 06:01 [medline]
PHST- 2022/10/01 00:00 [pmc-release]
AID - ad-13-5-1562 [pii]
AID - 10.14336/AD.2022.0224 [doi]
PST - epublish
SO  - Aging Dis. 2022 Oct 1;13(5):1562-1575. doi: 10.14336/AD.2022.0224. eCollection 
      2022 Oct 1.