Cell Membrane Modification for Rapid Display of Proteins as a Novel Means of Immunomodulation

Yolcu, Esma S.; Askenasy, Nadir; Singh, Narendra P.; Cherradi, Salah‐Eddine Lamhamedi; Shirwan, Haval

doi:10.1016/s1074-7613(02)00482-x

Cited by 88 publications

(176 citation statements)

References 38 publications

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“…Activated cells were then preincubated with a high concentration (4 g/ml) of SA-4-1BBL for 45 min on ice, washed extensively, and used for suppression assay. To differentiate between the proliferation of CD4 ϩ CD25 ϩ and CD4 ϩ CD25 Ϫ T cells in coculture experiments, CD4 ϩ CD25 Ϫ or CD4 ϩ CD25 ϩ T cells were labeled with CFSE (Molecular Probes) (43) and used in suppression assays as described. Proliferation was assessed using flow cytometry.…”

Section: Suppression Assaysmentioning

confidence: 99%

“…injection. Donor islets were harvested from fully mismatched C57BL/6 mice and transplantation was performed as previously described (43). Transplanted animals were monitored three times weekly and rejection confirmed by two consecutive blood glucose readings over 300 mg/dl.…”

Section: Islet Transplantationmentioning

confidence: 99%

“…In an attempt to use signaling via 4-1BB as an alternative to CD28-mediated costimulation for the expansion of Treg cells, we constructed a novel form of 4-1BBL chimeric with SA (SA-4-1BBL) that functions as a soluble protein. The rationale for using SA as the fusion partner stems from 1) the ability of SA to form tetramers and oligomers, and bind biotin, and 2) our observations that several SA chimeric molecules generated in our laboratory have potent immunological activities as compared with their native counterparts (42,43,48).…”

Section: Generation Of a Chimeric 4-1bbl Molecule Having Potent Costimentioning

confidence: 99%

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Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling

Elpek

Yolcu

Franke

et al. 2007

The Journal of Immunology

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143

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Naturally occurring CD4+CD25+FoxP3+ T regulatory (Treg) cells require three distinct signals transduced via TCR, CD28, and IL-2R for their development and maintenance. These requirements served as the basis for several recently developed ex vivo expansion protocols that relied on the use of solid support-bound Abs to CD3 and CD28 in the presence of high dose IL-2. We report in this study that Treg cells up-regulate the expression of inducible costimulatory receptor 4-1BB in response to IL-2, and stimulation using this receptor via a novel form of 4-1BB ligand (4-1BBL) fused to a modified form of core streptavidin (SA-4-1BBL) was effective in expanding these cells up to 110-fold within 3 wk. Expanded cells up-regulated CD25, 4-1BB, and membranous TGF-β, suppressed T cell proliferation, and prevented the rejection of allogeneic islets upon adoptive transfer into graft recipients. Importantly, SA-4-1BBL rendered CD4+CD25− T effector cells refractive to suppression by Treg cells. This dual function of signaling via 4-1BB, vis-à-vis Treg cell expansion and licensing T effector cells resistant to Treg cell suppression, as well as the up-regulation of 4-1BB by IL-2 may serve as important regulatory mechanisms for immune homeostasis following antigenic challenge. Stimulation using a soluble form of SA-4-1BBL represents a novel approach to expand Treg cells with potential therapeutic applications in autoimmunity and transplantation.

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Section: Suppression Assaysmentioning

confidence: 99%

Section: Islet Transplantationmentioning

confidence: 99%

Section: Generation Of a Chimeric 4-1bbl Molecule Having Potent Costimentioning

confidence: 99%

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Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling

Elpek

Yolcu

Franke

et al. 2007

The Journal of Immunology

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126

143

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“…16,43,49 Presentation of auto or transplantation antigens in conjunction with FasL leads to the activation of T cells and expression of Fas. Subsequent engagement of Fas with FasL on antigen-presenting cells (APCs) results in apoptosis of T cells ( Figure 3A-B).…”

Section: Systemic Immunomodulation With Faslmentioning

confidence: 99%

“…61 In contrast, Yolcu et al reported extended survival of allogeneic islets cotransplanted with allogeneic biotinylated splenocytes "decorated" with a metalloproteinase cleavage site-deficient FasL molecule chimeric with streptavidin (SA-FasL). 43 The main For personal use only. on May 10, 2018. by guest www.bloodjournal.org From functional differences between these modified molecules appeared to be their chemotactic effect on neutrophils.…”

mentioning

confidence: 99%

Induction of tolerance using Fas ligand: a double-edged immunomodulator

Askenasy

Yolcu

Yaniv

et al. 2005

Blood

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109

103

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Fas/FasL system and immune homeostasisThe immune system functions in complex and dynamic microenvironments, where decisions pertaining to the survival and/or physical elimination of antigen-specific T-cell clones are critical to the establishment and maintenance of functional immunity. Activationinduced cell death (AICD) is the primary homeostatic mechanism used by the immune system to control T-cell responses, promote tolerance to self-antigens, and prevent autoimmunity. [1][2][3] Following activation, T cells express Fas and Fas ligand (FasL) and upon repeated antigenic stimulation become sensitive to Fas/FasLmediated autocrine and paracrine apoptosis (Figure 1). [4][5][6] These 2 modes of apoptotic cell death serve to control the pool size of antigen-activated T-cell clones and regulate immune responses. 7 All lymphocytes, including CD4 ϩ and CD8 ϩ T, B, and natural killer (NK) cells as well as dendritic cells, monocytes, macrophages, and neutrophils are subject to Fas/FasL-regulated immune homeostasis. [8][9][10][11] Dysregulation of Fas/FasL-mediated AICD is associated with a series of pathophysiologic conditions, including degenerative and autoimmune disorders. 12 Mouse strains that lack Fas (lpr) or express a defective FasL molecule (gld) suffer from severe lymphoproliferative disorders and autoimmunity, 12,13 arising from the absence of antigen-induced clonal T-cell deletion in the periphery. 14,15 Similarly, the autoimmune lymphoproliferative syndrome in humans, an inherited disorder of lymphocyte homeostasis, is associated with the lack of AICD due to defects in Fas, FasL, and effector caspases. 16 Fas is a 45-kDa, type I cell surface protein with an extracellular domain that binds to FasL and a cytoplasmic domain that transduces the death signal. 17 Apoptosis is executed by the engagement and coaggregation of FasL with the Fas receptor on the cell surface followed by a series of intracellular molecular interactions that coordinate the hierarchical activation of caspases and cell death (Figure 2). Oligomerization of Fas following FasL engagement leads to the recruitment of Fas-associated proteins having death domains and the initiator procaspase-8 via its death effector domain into a death-inducing signaling complex (DISC). [18][19][20] Procaspase-8 undergoes autoproteolysis in the DISC complex to generate an active caspase-8, which in turn initiates extrinsic apoptosis by converting inactive effector procaspases-3, -6, and -7 into active enzymes via transproteolysis and intrinsic apoptosis via cleavage of Bid, release of cytochrome c, and activation of caspase-9. 18,21 Executioner caspases cleave various vital cellular substrates, which leads to cell death.FasL is a 40-kDa, type II cell surface protein that is inducibly expressed in lymphocytes, particularly T cells, 22 and constitutively expressed in cells present in immune privileged organs, such as Sertoli cells of the testis and epithelial cells in the eye. 23,24 Inasmuch as FasL-mediated apoptosis is critical to peripheral T-cell homeostasis...

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Local Immunomodulatory Strategies to Prevent Allo‐Rejection in Transplantation of Insulin‐Producing Cells

et al. 2021

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Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long-term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell-replacement strategies. Induction of local immunotolerance to prevent allo-rejection against islets and stem cell derived cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non-encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/ cell modification, immunomodulatory biomaterial platforms, and co-transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.

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Cell Membrane Modification for Rapid Display of Proteins as a Novel Means of Immunomodulation

Cited by 88 publications

References 38 publications

Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling

Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling

Induction of tolerance using Fas ligand: a double-edged immunomodulator

Local Immunomodulatory Strategies to Prevent Allo‐Rejection in Transplantation of Insulin‐Producing Cells

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