Arterial and venular endothelial cell costimulation of cytokine secretion by human T cell clones

Johnson, David R.; Hauser, Ingeborg A.; Voll, Reinhard; Emmrich, Frank

doi:10.1002/jlb.63.5.612

Cited by 22 publications

(15 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CTLL-2 cell line expresses the high-affinity mouse IL-2 receptor, the Kit-225 (K6) cell line expresses the high-affinity human IL-2 receptor (17), and the TF-1b cell line expresses only the intermediate-affinity human IL-2 receptor. For the Kit-225 assay, proliferation was measured by the reduction of Alamar Blue instead of 3 H thymidine uptake (18). Briefly, washed Kit-225 cells that had been starved for 4 days in AIM-V serum-free media (12,500 cells/well) were incubated with IL-2 or IL-2-containing immunocytokines for 36 hours.…”

Section: Il-2 Bioactivity Assaysmentioning

confidence: 99%

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

Gillies

Lan

Hettmann

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The goal of the study was to engineer a form of interleukin 2 (IL-2) that, when delivered as a tumor-specific antibody fusion protein, retains the ability to stimulate an antitumor immune response via interaction with the high-affinity IL-2 receptor but has lower toxicity because of the reduced activation of the intermediate-affinity IL-2 receptor.Experimental Design: We investigated changes in the proposed toxin motif of IL-2 by introducing a D20T mutation that has little effect on the activity of free IL-2. We expressed this IL-2 variant as a fusion protein with an antibody (NHS76) that targets the necrotic core of tumors and characterized this molecule (NHS-IL2LT) in vitro and in vivo.Results: NHS-IL2LT was shown to have near normal biological activity in vitro by using T-cell lines expressing the high-affinity IL-2 receptor, but little or no activity by using cell lines expressing only the intermediate IL-2 receptor. Relative to the control antibody fusion protein containing wild-type IL-2, NHS-IL2LT retained antitumor activity against established neuroblastoma and non-small cell lung cancer metastases in syngeneic mouse tumor models but was much better tolerated in immune-competent mice and in cynomolgus monkeys.Conclusions: The qualities of low toxicity and single-agent efficacy shown suggest that NHS-IL2LT is a good candidate for therapeutic approaches combining standard cytotoxic and immune therapies. In fact, this molecule (also known as Selectikine or EMD 521873) is currently in phase I clinical trial. Clin Cancer Res; 17(11); 3673-85. Ó2011 AACR.

show abstract

Section: Il-2 Bioactivity Assaysmentioning

confidence: 99%

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

Gillies

Lan

Hettmann

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Microvascular ECs in humans and other large mammals express both class I and class II major histocompatibility complex (MHC-I and MHC-II, respectively) molecules on their surfaces in vivo (64) and regularly come into contact with circulating lymphocytes within the microvasculature, especially within capillaries and venules (49). Cultured ECs provide antigenic stimulation and costimulation to resting memory T cells, resulting in proliferation and cytokine elaboration (28,31,37). Cultured human ECs, left untreated, lose MHC-II expression; however, gamma interferon (IFN-␥) restores this expression so that ECs can acquire, process, and present antigen in a manner that effectively activates resting peripheral blood CD4 ϩ T cells and T-cell clones (40,52,53,56).…”

Section: Although Cd4mentioning

confidence: 99%

Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4⁺T Cells in a Nef-Dependent Manner In Vitro and In Vivo

Choi¹,

Walker²,

Boichuk

et al. 2005

J Virol

View full text Add to dashboard Cite

show abstract

“…Antigen recognition can produce tolerance or aggression, depending on the precise interactions between T cells and APCs. Several groups have shown that ECs from different vascular beds are capable of performing certain APC functions in vitro [52,62,97,98]. However, EC activities as APCs in vivo are poorly defined.…”

Section: Research Approachesmentioning

confidence: 99%

“…Similarly, activated T cells migrate to an inflammation and not lymph nodes [61]. Iliac ECs or human umbilical vein ECs (HUVEC) activated with TNF do not costimulate T cells better despite significant increases in cell adhesion molecule expression [52]. EC activation actually decreases CD8+ T cell costimulation and transendothelial migration in vitro [62].…”

Section: T Cell Recruitmentmentioning

confidence: 99%

See 1 more Smart Citation

Endothelial Cell-Mediated Antigen Presentation

Johnson¹

2006

Transfus Med Hemother

Self Cite

View full text Add to dashboard Cite

Immune recognition of endothelial cells (ECs) has been implicated in a number of vascular diseases. Although ECs have been shown to stimulate T lymphocytes in vitro, these conditions were not physiological, and it remained unclear what occurred in vivo. Antigen presentation by ECs in vivo was tested using transgenic mice that express a protein antigen (ß-galactosidase, ß-gal) exclusively in their ECs. This transgenic approach avoided potentially inflammatory manipulations. Transgenic mice responded to immunization with the antigen (protein or DNA) with strong B and T cell-mediated immunity. No effects of the immune response on the vessels in vivo could be detected, and ECs continued to express ß-gal. Skin grafts from transgenic mice onto nontransgenic mice suffered a type of vascular rejection, strongly suggesting that specific lymphocytes in hosts recognize and respond against ß-gal+ ECs in the skin grafts. However, heart transplants containing ß-gal+ ECs were accepted indefinitely by nontransgenic hosts. Moreover, skin grafts with ß-gal+ ECs were accepted onto hosts with hearts containing ß-gal+ ECs, suggesting that the immune system had recognized and learned to tolerate the heart ECs. The implications for transplantation and persistent infection are discussed.

show abstract

Arterial and venular endothelial cell costimulation of cytokine secretion by human T cell clones

Cited by 22 publications

References 51 publications

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4⁺T Cells in a Nef-Dependent Manner In Vitro and In Vivo

Endothelial Cell-Mediated Antigen Presentation

Contact Info

Product

Resources

About

Arterial and venular endothelial cell costimulation of cytokine secretion by human T cell clones

Cited by 22 publications

References 51 publications

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

A Low-Toxicity IL-2–Based Immunocytokine Retains Antitumor Activity Despite Its High Degree of IL-2 Receptor Selectivity

Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4+T Cells in a Nef-Dependent Manner In Vitro and In Vivo

Endothelial Cell-Mediated Antigen Presentation

Contact Info

Product

Resources

About

Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4⁺T Cells in a Nef-Dependent Manner In Vitro and In Vivo