Identification of the immunodominant CTL epitope of EGFP in C57BL/6 mice

Han, Wanda G. H.; Unger, Wendy W. J.; Wauben, Marca H. M.

doi:10.1038/sj.gt.3303104

Cited by 29 publications

(29 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although it has been shown that EGFP is less immunogenic in C57BL/6 mice in comparison with BALB/c mice, Han et al were able to identify an immunodominant CTL epitope of EGFP that induced specific CTL responses in C75Bl/6 (Han et al 2008). GFP-expressing DCs transduced with an adenovirus not only promotes dendritic cell maturation, but also elicits GFPspecific cellular immune responses (Re et al 2004).…”

Section: Discussionmentioning

confidence: 95%

“…Immunogenicity of a protein is influenced by many factors, including type of host cell used as source of protein expression, type of expression and delivery system of the protein, conformation of expressed protein, type of parasite, antigen dose dependency in cell/tissue, persistent expression of protein, and host factors such as the genetic background (Han et al 2008). In this study, we used two different sources for EGFP protein, a live parasite cell that constitutively expresses and enhances expression level during infection and a recombinant EGFP in a limited and stable level and without change during infection in mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice

Seif

Kazemi

Gholami

et al. 2015

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Optical reporter genes such as green fluorescent protein (GFP) and luciferase are efficiently and widely used in monitoring and studying the protective/therapeutic potential of candidate agents in leishmaniasis. But several observations and controversial reports have generated a main concern, whether enhanced GFP (EGFP) affects immune response. To address this issue, we studied the immunogenicity of EGFP in vivo by two lines of stably transfected parasites (Leishmania major (EGFP) or L. major (EGFP-LUC)) in BALB/c model and/or as a recombinant protein (rEGFP) produced in vitro by bacteria in parallel. Disease progression was followed by footpad swelling measurements and parasite burden in draining lymph nodes using microtitration assay and real-time PCR, and immune responses were also evaluated in spleen. EGFP-expressing parasites generated larger swellings in comparison with wild-type (L. major) while mice immunized with rEGFP and challenged with wild-type parasite were quite comparable in footpad swelling with control group without significant difference. However, both conventional and molecular approaches revealed no significant difference in parasite load between different groups. More importantly, no significant inflammatory responses were detected in groups with higher swelling size measured by interferon-γ (IFN-γ), interleukin (IL)-10, IL-5, and nitric oxide against frozen and thawed lysate of parasite as stimulator. Altogether, these results clearly revealed that EGFP protein expressed in prokaryotic and eukaryotic hosts is not an immunological reactive molecule and acts as a neutral protein without any side effects in mice. So, EGFP expressing Leishmania could be a safe and reliable substitution for wild-types that simplifies in situ follow-up and eliminates the animal scarification wherever needed during the study.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice

Seif

Kazemi

Gholami

et al. 2015

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…To test the possibility that GFP can serve as a transplantation antigen (16,17), we assessed the relative persistence of a mix of RTEs and MN T cells cotransferred both to GFP + recipients and to recipients that were GFP − but were primed with GFP + cells. Regardless of whether the recipients expressed or were primed to GFP, CD4 and CD8 RTEs declined to the same degree relative to their MN counterparts 3 wk after transfer (Fig.…”

Section: Resultsmentioning

confidence: 99%

Recent thymic emigrants are preferentially incorporated only into the depleted T-cell pool

Houston¹,

Higdon

Fink³

2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, and they differ functionally and phenotypically from the rest of the naïve T-cell pool. RTEs are present in the peripheral T-cell pool throughout life but are the most common subset of T cells in neonates and adults recovering from lymphoablation. Using a murine model to study the homeostasis of RTEs, we show that under lymphoreplete conditions, RTEs are at a competitive disadvantage to already established mature naïve (MN) T cells. This disadvantage may be caused by a defect in survival, because RTEs may transduce homeostatic signals inefficiently, and their ability to survive is enhanced with increased expression of IL-7 receptor or B-cell lymphoma 2 (Bcl-2). Conversely, under lymphopenic conditions, enhanced proliferation by RTEs allows them to out-compete their MN T-cell counterparts. These results suggest that in times of need, such as in neonates or lymphopenic adults, RTEs perform well to fill the gaps in the peripheral T-cell pool, but when the periphery already is full, many RTEs are not incorporated into the pool of recirculating lymphocytes. R ecent thymic emigrants (RTEs) are the youngest subset of naïve T cells, those that recently have entered the lymphoid periphery after development in the thymus. RTEs maintain T-cell diversity in the periphery (1), a particularly important contribution in the very young and in adults recovering from lymphopenia.The original paradigm held that the thymus minted fully functional T cells. However, it is becoming clear that RTEs in both humans and mice undergo postthymic maturation in the lymphoid periphery (2-6) before joining the mature naïve (MN) T-cell pool. RTEs and MN T cells differ in surface phenotype, and, as compared with MN T cells, stimulated RTEs generally proliferate less and secrete less cytokine. Studying RTEs has been facilitated by the characterization of a transgenic (Tg) model system (7) that allows unambiguous identification and live-cell purification of this subset. In mice Tg for GFP under control of the recombination activating gene 2 promoter (RAG2p-GFP Tg mice), RTEs are GFP + peripheral T cells (2). The GFP label is brightest in the youngest RTEs (8) and decays over time until it can no longer be detected on T cells that have been in the lymphoid periphery for more than 3 wk (2).Throughout life, the peripheral T-cell pool is maintained at a relatively constant size despite continuous turnover and thymic export of about 1 × 10 6 cells per day (9, 10). The T-cell pool is maintained at a size large enough to protect adequately against pathogens, with estimated 1 × 10 6 antigen specificities (11), but small enough to avoid taxing the host's resources. Homeostasis is maintained by competition for two limiting factors, IL-7 and MHC loaded with self-peptides (12, 13).Lymphopenia occurs in humans in a variety of clinical and disease settings, including after stem cell transplantation, chemotherapy, and HIV infection. Under lymphopenic conditions, the remaining peripheral ...

show abstract

“…However, these B6 iPSC-derived skin tissues have already been preselected by the B6 immune system in the chimeric mice, and thus the skin graft will not be rejected by B6 immune system when transplanted onto new B6 mice. In support of this notion, GFP is a foreign protein and immunogenic to B6 mice when expressed in the skin, and GFP-expressing skin tissues of GFP transgenic B6 mice are immune rejected when grafted to the B6 mice (36–38). …”

Section: The Immunogenicity Of Ipscs and Their Derivativesmentioning

confidence: 94%

The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives

Liu

et al. 2017

Front. Immunol.

128

View full text Add to dashboard Cite

Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient. The breakthrough of the technology to generate autologous-induced pluripotent stem cells (iPSCs) by nuclear reprogramming of patient’s somatic cells raised the possibility that autologous iPSC-derived cells can be transplanted into the patients without the concern of immune rejection. However, accumulating data indicate that certain iPSC-derived cells can be immunogenic. In addition, the genomic instability associated with iPSCs raises additional safety concern to use iPSC-derived cells in human cell therapy. In this review, we will discuss the mechanism underlying the immunogenicity of the pluripotent stem cells and recent progress in developing immune tolerance strategies of human pluripotent stem cell (hPSC)-derived allografts. The successful development of safe and effective immune tolerance strategy will greatly facilitate the clinical development of hPSC-based cell therapy.

show abstract

Identification of the immunodominant CTL epitope of EGFP in C57BL/6 mice

Cited by 29 publications

References 10 publications

EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice

EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice

Recent thymic emigrants are preferentially incorporated only into the depleted T-cell pool

The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives

Contact Info

Product

Resources

About