scholarly journals Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis

Hepatology ◽  
2008 ◽  
Vol 47 (2) ◽  
pp. 581-591 ◽  
Author(s):  
Maria Serena Longhi ◽  
Francesca Meda ◽  
Pengyun Wang ◽  
Marianne Samyn ◽  
Giorgina Mieli-Vergani ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis ◽  
De Novo

scholarly journals Inflammasome Priming Mediated via Toll-Like Receptors 2 and 4, Induces Th1-Like Regulatory T Cells in De Novo Autoimmune Hepatitis

2018 ◽  
Vol 9 ◽  
Author(s):  
Adam S. Arterbery ◽  
Jie Yao ◽  
Andrew Ling ◽  
Yaron Avitzur ◽  
Mercedes Martinez ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis ◽  
De Novo ◽  
Toll Like Receptors

scholarly journals Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells

2016 ◽  
Vol 196 (10) ◽  
pp. 4040-4051 ◽  
Author(s):  
Adam S. Arterbery ◽  
Awo Osafo-Addo ◽  
Yaron Avitzur ◽  
Maria Ciarleglio ◽  
Yanhong Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis ◽  
Proinflammatory Cytokines ◽  
De Novo

Mesenchymal stem cells induce the expansion of regulatory T cells in abortion-prone mice

Reproduction ◽  
2021 ◽  
Author(s):  
Amir Salek Farrokhi ◽  
Amir-Hassan Zarnani ◽  
Fatemeh Rezaei kahmini ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
De Novo ◽  
Abortion Rate ◽  
Cellular Mechanisms ◽  
Inguinal Lymph Nodes

Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, and Ho1, Foxp3, Pd1, and Ctla4 genes expression at the feto-maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT- PCR, respectively. The abortion rate in MSCs-treated mice was significantly reduced and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of HO1, Foxp3, Pd1, and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and up-regulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

scholarly journals Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

2017 ◽  
Vol 47 (12) ◽  
pp. 2142-2152 ◽  
Author(s):  
Maria Pasztoi ◽  
Joern Pezoldt ◽  
Michael Beckstette ◽  
Christoph Lipps ◽  
Dagmar Wirth ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Regulatory T Cells ◽  
Extracellular Vesicles ◽  
Mesenteric Lymph Node ◽  
Stromal Cell ◽  
De Novo ◽  
Mesenteric Lymph

scholarly journals Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung-Restricted Autoimmunity

2016 ◽  
Vol 197 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Stephen Chiu ◽  
Ramiro Fernandez ◽  
Vijay Subramanian ◽  
Haiying Sun ◽  
Malcolm M. DeCamp ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lung Injury ◽  
De Novo

scholarly journals Attenuation of Experimental Autoimmune Hepatitis by Exogenous and Endogenous Cannabinoids: Involvement of Regulatory T Cells

2008 ◽  
Vol 74 (1) ◽  
pp. 20-33 ◽  
Author(s):  
Venkatesh L. Hegde ◽  
Shweta Hegde ◽  
Benjamin F. Cravatt ◽  
Lorne J. Hofseth ◽  
Mitzi Nagarkatti ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis ◽  
Endogenous Cannabinoids ◽  
Experimental Autoimmune

scholarly journals De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells

2005 ◽  
Vol 102 (11) ◽  
pp. 4103-4108 ◽  
Author(s):  
M. R. Walker ◽  
B. D. Carson ◽  
G. T. Nepom ◽  
S. F. Ziegler ◽  
J. H. Buckner
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
De Novo

FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency

2012 ◽  
Vol 57 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Moritz Peiseler ◽  
Marcial Sebode ◽  
Björn Franke ◽  
Frederike Wortmann ◽  
Dorothee Schwinge ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis

scholarly journals PMO-137 Phenotypic and functional signature of CD4POSCD25HIGHCD127 low regulatory T-cells in autoimmune hepatitis

Gut ◽  
2012 ◽  
Vol 61 (Suppl 2) ◽  
pp. A128.2-A129
Author(s):  
R Liberal ◽  
C Grant ◽  
G Mieli-Vergani ◽  
D Vergani ◽  
M Longhi
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Hepatitis

Homeostatic Expansion of Donor FoxP3+ CD25+CD4+ T Cells in Recipients of CD4+ Cells Depleted Allogeneic Hematopoietic Graft.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3207-3207
Author(s):  
Mohammad S. Hossain ◽  
Cynthia R. Giver ◽  
Ned Waller
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
Stem Cell ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
De Novo ◽  
Clinical Signs ◽  
Post Transplant ◽  
Allogeneic Bmt ◽  
Homeostatic Expansion

Abstract Background: In allogeneic BMT patients, the presence of allo-reactive donor CD4+ T cells in the graft were reported to be the primary cause of GvHD. Moreover, donor T-cells are required to promote the stem cell engraftment and to decrease the disease relapse. A number of studies also reported that a subset of CD4+CD25+ T cells usually generated de novo from the thymus that expressed FoxP3 regulate the T cells allo-reactivity in vivo. Thus, to establish a therapeutically useful adoptive T-cells immunotherapy, we depleted the CD4+ T cells from the graft and transplanted along with T cell depleted (TCD) BM cells in clinically relevant parent to F1 experimental allogeneic BMT model. Our hypothesis is that CD4-depleted graft will not cause GvHD, preserve the thymic function, homeostatically produce donor BM-derived CD4+ T cells along with FoxP3+CD4+CD25+ regulatory T cells with beneficial anti-opportunistic infection and anti-tumor effects. Methods: We used a parent (C57BL/6) to (C57BL/6 X BALB/c)CB6F1 allogeneic BMT model with a combination of TCD BM and splenocytes as the hematopoietic graft. CD4+ or CD8+ cells were selectively depleted from the splenocytes of C57BL/6 donor mice using MACS column. 1×106 CD4-depleted splenocytes or a mixture of 2×106 CD8-depleted and 1×106 CD4-depleted splenocytes and/or grafts containing 10×106 unfractionated splenocytes along with 5×106 TCD BM cells harvested from the congeneic C57BL/6 donor mice, were adoptively transferred to lethally irradiated (11Gy) CB6F1 mice. GvHD was monitored twice weekly by weight loss and other clinical signs. After 50 days post transplant recipients mice were bled or sacrificed and lymphocytes isolated from blood and different organs were analyzed by multicolor FACS. Results: Within 50 days of transplant the recipients of CD4-depleted splenocytes had 100% survival without GvHD whereas recipients of mixture of CD4- and CD8-depleted splenocytes or unfractionated splenocytes suffered from severe GvHD (%weight loss below 20%) with 50% survival. Surprisingly, very significantly expansion of total CD4+ T cells (37% ± 7% of lymphocytes, CD4:CD8 ratio 6:1) occurred in the blood of recipients of CD4-depleted splenocytes. In contrast the recipients of mixture of CD4- and CD8-depleted splenocytes DLI or whole splenocytes had only few CD4+ T cells (~2% ± 2% of lymphocytes, CD4:CD8 ratio 1:2). Over 90% of the CD4+ T cells in the blood of recipients of CD4-depleted splenocytes were from the donor BM and included significantly higher number of CD25+CD4+ T cells compared with the recipients of mixture of CD4- and CD8-depleted splenocytes or unfractionated splenocytes. Similarly, significantly increased numbers of FoxP3+CD25+CD4+ regularity T cells were also found in the spleen and thymus of recipients of CD4-depleted splenocytes compared with the recipients of mixture of CD4- and CD8-depleted splenocytes or unfractionated splenocytes (p<0.005). Conclusion: Adoptive immunotherapy with the CD4-depleted hematopoietic graft results better immune reconstitution, caused extensive homeostatic expansion of donor stem cell-derived CD4+ T cells including significantly increased levels of FoxP3+CD25+ CD4+ regulatory T cells derived from de novo thymopoiesis without GvHD. The presence of donor FoxP3+CD25+ CD4+ regulatory T cells in the hematopoietic graft are not necessary for post-transplant expansion of donor stem-cell-derived regulatory T-cells via thymopoiesis.

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