scholarly journals C5aR1 regulates migration of suppressive myeloid cells required for costimulatory blockade‐induced murine allograft survival

2018 ◽  
Vol 19 (3) ◽  
pp. 633-645 ◽  
Author(s):  
Ines Llaudo ◽  
Miguel Fribourg ◽  
M. Edward Medof ◽  
Patricia Conde ◽  
Jordi Ochando ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Allograft Survival ◽  
Costimulatory Blockade

scholarly journals Costimulatory Blockade-Induced Allograft Survival Requires Beclin1

2014 ◽  
Vol 14 (3) ◽  
pp. 545-553 ◽  
Author(s):  
D. A. Verghese ◽  
A. Yadav ◽  
P. Bizargity ◽  
B. Murphy ◽  
P. S. Heeger ◽  
...  
Keyword(s):  
Allograft Survival ◽  
Costimulatory Blockade

scholarly journals Berberine Promotes Induction of Immunological Tolerance to an Allograft via Downregulating Memory CD8+ T-Cells Through Altering the Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Feifei Qiu ◽  
Weihui Lu ◽  
Shulin Ye ◽  
Huazhen Liu ◽  
Qiaohuang Zeng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gut Microbiota ◽  
Memory T Cells ◽  
Transplant Rejection ◽  
Therapeutic Effects ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Costimulatory Blockade

Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections.

scholarly journals Neutralizing IL-7 Promotes Long-Term Allograft Survival Induced by CD40/CD40L Costimulatory Blockade

2006 ◽  
Vol 6 (12) ◽  
pp. 2851-2860 ◽  
Author(s):  
Y. Wang ◽  
H. Dai ◽  
Z. Liu ◽  
X. Cheng ◽  
G. Tellides ◽  
...  
Keyword(s):  
Allograft Survival ◽  
Costimulatory Blockade

scholarly journals CD8+CD122+PD-1+ Tregs Synergize With Costimulatory Blockade of CD40/CD154, but Not B7/CD28, to Prolong Murine Allograft Survival

2019 ◽  
Vol 10 ◽  
Author(s):  
Huazhen Liu ◽  
Feifei Qiu ◽  
Yuanzhong Wang ◽  
Qiaohuang Zeng ◽  
Cuihua Liu ◽  
...  
Keyword(s):  
Allograft Survival ◽  
Costimulatory Blockade

scholarly journals Bone Marrow-Derived AXL Tyrosine Kinase Promotes Mitogenic Crosstalk and Cardiac Allograft Vasculopathy

2021 ◽  
Author(s):  
Kristofor Glinton ◽  
Matthew DeBerge ◽  
Emily Fisher ◽  
Samantha Schroth ◽  
Arjun Sinha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Immune Cell ◽  
Myeloid Cells ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Cell Surface Receptor ◽  
Standards Of Care ◽  
Allograft Survival ◽  
Allograft Vasculopathy

ABSTRACTCardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. AXL protein is found on multiple cell types, including bone marrow-derived myeloid cells. The causal role of AXL from this compartment and during transplant is largely unknown. This is important because AXL is a key regulator of myeloid inflammation. Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene, we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. Co-culture experiments designed to identify cell-intrinsic functions of Axl uncovered complementary cell-proliferative pathways by which Axl promotes CAV-associated inflammation. Specifically, Axl-deficient myeloid cells were less efficient at increasing the replication of both antigen-specific T cells and vascular smooth muscle cells (VSMCs), the latter a key hallmark of CAV. For the latter, we discovered that Axl-was required to amass the VSMC mitogen Platelet-Derived Growth Factor. Taken together, our studies reveal a new role for myeloid Axl in the progression of CAV and mitogenic crosstalk. Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival.

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