Prolonged Xenograft Survival Induced by Inducible Costimulator-Ig Is Associated With Increased Forkhead Box P3+ Cells

Hodgson, Russell; Christiansen, Dale; Ziolkowski, Andrew; Mouhtouris, Effie; Simeonovic, Charmaine J.; Ierino, Francesco L.; Sandrin, Mauro S.

doi:10.1097/tp.0b013e31821774e0

Cited by 11 publications

(20 citation statements)

References 48 publications

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“…Each buffer was used according to the manufacturer instructions. We observed that fixation/permeabilization buffers affected the SSC/FSC characteristics of the cells (Figure 1, row 1), and this result was identical to the staining results of human Treg cell (Hodgson et al, 2011). The CD3 staining was consistent, with 23 to 37% of CD3 + events in the lymphocyte gate of PBMCs and 22 to 29% in the spleen lymphocyte gate (Figure 1, row 2).…”

Section: Comparison Of Fixation/permeabilization Bufferssupporting

confidence: 72%

“…+ (Hodgson et al, 2011). Several publications noted concerns about the influence of different clones of Foxp3 antibodies coupled to different fluorochromes and paired with different fixation/permeabilization buffers on the staining of human Treg cells (Tran et al, 2007;Pillai and Karandikar, 2008;Grant et al, 2009;Law et al, 2009;Presicce et al, 2010).…”

Section: Cd4mentioning

confidence: 99%

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Application and effects of mouse Foxp3 antibody and fixation/permeabilization buffer on the detection of CD4+ regulatory T cells in various mammal species

Sun

Lin²,

Zhang³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. CD4+ regulatory T lymphocytes (Treg cells) play a crucial role in maintaining the normal immune homeostasis. Foxp3, as a key marker for Treg cells, is widely used to identify Treg cells, not only in humans but also in other species, like mouse, porcine, ovine, and bovine. To detect reproducible Treg cells is important for evaluating the state of the immune system, and thus, it is necessary to optimize Foxp3 staining. Here, we present a comparative study of MF23 and FJK-16s clones of anti-mouse Foxp3 antibodies, used in combination with two different fixation/permeabilization buffers. For Foxp3 staining, the fixation/permeabilization buffer and Foxp3 antibody FJK-16s clone from eBioscience were better than those from BD Pharmingen, with the best fluorochrome PE. Moreover, when using the best combination, there was a highly significant positive correlation between CD25 + T cells + T cells. Therefore, the CD25 marker can be used as an alternative to the Foxp3 antibody. As FJK-16s is also applicable for detecting bovine, porcine, canine, ovine, and equine Foxp3 antibodies, these results will be helpful not only in quantifying the frequencies of mouse Treg cells, but also in accurately detecting Treg cells of the other species mentioned above by multicolor flow cytometry.

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Section: Comparison Of Fixation/permeabilization Bufferssupporting

confidence: 72%

Section: Cd4mentioning

confidence: 99%

Application and effects of mouse Foxp3 antibody and fixation/permeabilization buffer on the detection of CD4+ regulatory T cells in various mammal species

Sun

Lin²,

Zhang³

et al. 2013

Genet. Mol. Res.

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“…The in vivo infusion of hPD-L1 þ endothelial cells prolongs the survival of porcine skin grafts, favoring the expansion of Foxp3 þ CD4 þ T cells (Ding et al 2011). Much the same results have been obtained in mice by grafting porcine endothelial cells transfected with ICOS-Ig, a soluble form of ICOS (Hodgson et al 2011), suggesting that Treg-based strategies may represent a novel path toward achieving tolerance in xenotransplantation.…”

Section: T-cell Tolerance and Tregsvsupporting

confidence: 65%

Immunological Challenges and Therapies in Xenotransplantation

Vadori

2014

Cold Spring Harbor Perspectives in Medicine

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“…The effects of ICOS on the functions of T cell are mainly initiated by the interaction between ICOS and its ligand (B7 related protein 1, B7RP1 or ICOSL), which is generally expressed on diverse antigen presenting cells (APC) [2]. ICOS-related signal plays important roles in many T cell-mediated disease models, such as inflammation [3], anti-viral immune responses [4], anti-tumor immune responses [5], allogeneic grafts rejection [6,7], wound healing [8], and thus representing a potential target of treatment [9]. However, the roles of ICOS-ICOSL interaction in human immune system are still inclusive.…”

Section: Introductionmentioning

confidence: 99%

ICOS Regulates the Generation and Function of Human CD4+ Treg in a CTLA-4 Dependent Manner

et al. 2013

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Inducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4.

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Prolonged Xenograft Survival Induced by Inducible Costimulator-Ig Is Associated With Increased Forkhead Box P3+ Cells

Abstract: This study demonstrates prolonged xenograft survival by local expression of ICOS-Ig, we propose that the accumulation of CD4(+)CD25(+)Foxp3(+) cells at the periphery of the graft and secretion of interleukin-10 is responsible for this novel observation.

Cited by 11 publications

References 48 publications

Application and effects of mouse Foxp3 antibody and fixation/permeabilization buffer on the detection of CD4+ regulatory T cells in various mammal species

Application and effects of mouse Foxp3 antibody and fixation/permeabilization buffer on the detection of CD4+ regulatory T cells in various mammal species

Immunological Challenges and Therapies in Xenotransplantation

ICOS Regulates the Generation and Function of Human CD4+ Treg in a CTLA-4 Dependent Manner

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