PMID- 30944247
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20200629
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 4
IP  - 7
DP  - 2019 Apr 4
TI  - Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated 
      lymphoablation.
LID - 125489 [pii]
LID - 10.1172/jci.insight.125489 [doi]
LID - e125489
AB  - Antibody-mediated lymphoablation is used in solid organ and stem cell 
      transplantation and autoimmunity. Using murine anti-thymocyte globulin (mATG) in 
      a mouse model of heart transplantation, we previously reported that the 
      homeostatic recovery of CD8+ T cells requires help from depletion-resistant 
      memory CD4+ T cells delivered through CD40-expressing B cells. This study 
      investigated the mechanisms by which B cells mediate CD8+ T cell proliferation in 
      lymphopenic hosts. While CD8+ T cell recovery required MHC class I expression in 
      the host, the reconstitution occurred independently of MHC class I, MHC class II, 
      or CD80/CD86 expression on B cells. mATG lymphoablation upregulated the B cell 
      expression of several cytokine genes, including IL-15 and IL-27, in a 
      CD4-dependent manner. Neither treatment with anti-CD122 mAb nor the use of 
      IL-15Ralpha-/- recipients altered CD8+ T cell recovery after mATG treatment, 
      indicating that IL-15 may be dispensable for T cell proliferation in our model. 
      Instead, IL-27 neutralization or the use of IL-27Ralpha-/- CD8+ T cells inhibited 
      CD8+ T cell proliferation and altered the phenotype and cytokine profile of 
      reconstituted CD8+ T cells. Our findings uncover what we believe is a novel role 
      of IL-27 in lymphopenia-induced CD8+ T cell proliferation and suggest that 
      targeting B cell-derived cytokines may increase the efficacy of lymphoablation 
      and improve transplant outcomes.
FAU - Ayasoufi, Katayoun
AU  - Ayasoufi K
FAU - Zwick, Daniel B
AU  - Zwick DB
FAU - Fan, Ran
AU  - Fan R
FAU - Hasgur, Suheyla
AU  - Hasgur S
FAU - Nicosia, Michael
AU  - Nicosia M
FAU - Gorbacheva, Victoria
AU  - Gorbacheva V
FAU - Keslar, Karen S
AU  - Keslar KS
FAU - Min, Booki
AU  - Min B
FAU - Fairchild, Robert L
AU  - Fairchild RL
FAU - Valujskikh, Anna
AU  - Valujskikh A
LA  - eng
GR  - U01 AI063594/AI/NIAID NIH HHS/United States
GR  - R01 AI113142/AI/NIAID NIH HHS/United States
GR  - T32 CA217836/CA/NCI NIH HHS/United States
GR  - R21 AI121524/AI/NIAID NIH HHS/United States
GR  - R01 AI125247/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190404
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Il27 protein, mouse)
RN  - 0 (Interleukins)
RN  - D7RD81HE4W (thymoglobulin)
RN  - T-Lymphocytopenia
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antilymphocyte Serum/*administration & dosage
MH  - B-Lymphocytes/immunology/metabolism
MH  - Bone Marrow Transplantation
MH  - CD4-Positive T-Lymphocytes/immunology/transplantation
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Female
MH  - Graft Rejection/*immunology/prevention & control
MH  - Heart Transplantation/adverse effects
MH  - Humans
MH  - Immunologic Memory
MH  - Interleukins/antagonists & inhibitors/immunology/*metabolism
MH  - Lymphocyte Depletion/methods
MH  - Lymphopenia/chemically induced/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Transplantation Chimera
MH  - Up-Regulation/immunology
PMC - PMC6483639
OTO - NOTNLM
OT  - B cells
OT  - Cytokines
OT  - Immunology
OT  - T cells
OT  - Transplantation
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2019/04/05 06:00
MHDA- 2020/07/01 06:00
PMCR- 2019/04/04
CRDT- 2019/04/05 06:00
PHST- 2018/10/11 00:00 [received]
PHST- 2019/02/26 00:00 [accepted]
PHST- 2019/04/05 06:00 [entrez]
PHST- 2019/04/05 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/04/04 00:00 [pmc-release]
AID - 125489 [pii]
AID - 10.1172/jci.insight.125489 [doi]
PST - epublish
SO  - JCI Insight. 2019 Apr 4;4(7):e125489. doi: 10.1172/jci.insight.125489. 
      eCollection 2019 Apr 4.