Transduction with Human Telomerase Reverse Transcriptase Immortalizes A Rhesus Macaque CD8+T Cell Clone with Maintenance of Surface Marker Phenotype And Function

2007 ◽  
Vol 23 (3) ◽  
pp. 456-465 ◽  
Author(s):  
Hanne Andersen ◽  
Eugene V. Barsov ◽  
Matthew T. Trivett ◽  
Charles M. Trubey ◽  
Luis D. Giavedoni ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Surface Marker ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
T Cell Clone ◽  
Human Telomerase ◽  
And Function ◽  
Marker Phenotype

Targeting human telomerase reverse transcriptase with recombinant lentivector is highly effective to stimulate antitumor CD8 T-cell immunity in vivo

Blood ◽  
2010 ◽  
Vol 115 (15) ◽  
pp. 3025-3032 ◽  
Author(s):  
Olivier Adotévi ◽  
Karine Mollier ◽  
Christine Neuveut ◽  
Magalie Dosset ◽  
Patrice Ravel ◽  
...  
Keyword(s):  
T Cell ◽  
Reverse Transcriptase ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Active Immunotherapy ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Cell Immunity ◽  
Human Telomerase

Abstract The success of active immunotherapy is based on the vaccine's ability to overcome immune tolerance through recalibrating the immune system so that it is able to recognize tumor antigens as foreign rather than self. In this study, we used a lentiviral vector system to target human telomerase reverse transcriptase (lv-hTERT), a widely expressed tumor antigen. Immunization of HLA-A*0201 transgenic HHD mice with recombinant lv-hTERT vector induces potent and diversified cytotoxic T lymphocyte responses that recognize in vitro murine tumor cells, which overexpress telomerase. Compared with peptide-based vaccinations, the lv-hTERT vector triggers better and more sustained CD8+ T-cell response against self/TERT epitope in vivo. The study found that the additional use of a heterologous boosted vaccination drastically improves self/TERT-specific CD8 responses in lv-hTERT primed mice. Both primary and long-lasting self/TERT-specific CD8+ T-cell responses induced with Iv-hTERT vector required the presence of CD4 T cells in vivo. This lv-hTERT–based active immunotherapy efficiently inhibits the growth of telomerase expressing tumors (B16/HLA-A2.1 murine melanoma) in HHD mice. These data show that targeting hTERT with lentivector is highly effective in stimulating a broad range of CD8 T-cell immunity that can be exploited for cancer immunotherapy.

scholarly journals A porcine CD8+ T Cell Clone with Heterotypic Specificity for Foot-and-mouth Disease Virus

1996 ◽  
Vol 77 (9) ◽  
pp. 2089-2096 ◽  
Author(s):  
A. Rodriguez ◽  
V. Ley ◽  
E. Ortuno ◽  
A. Ezquerra ◽  
A. Saalmuller ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Virus ◽  
Cell Clone ◽  
Foot And Mouth Disease ◽  
Cd8 T Cell ◽  
Mouth Disease ◽  
T Cell Clone ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals IL4I1 Accelerates the Expansion of Effector CD8+ T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Marie-Line Puiffe ◽  
Aurélie Dupont ◽  
Nouhoum Sako ◽  
Jérôme Gatineau ◽  
José L. Cohen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Clone

IL4I1 is an immunoregulatory enzyme that inhibits CD8 T-cell proliferation in vitro and in the tumoral context. Here, we dissected the effect of IL4I1 on CD8 T-cell priming by studying the differentiation of a transgenic CD8 T-cell clone and the endogenous repertoire in a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. Unexpectedly, we show that IL4I1 accelerates the expansion of functional effector CD8 T cells during the first several days after infection and increases the average affinity of the elicited repertoire, supporting more efficient LCMV clearance in WT mice than IL4I1-deficient mice. Conversely, IL4I1 restrains the differentiation of CD8 T-cells into long-lived memory precursors and favors the memory response to the most immunodominant peptides. IL4I1 expression does not affect the phenotype or antigen-presenting functions of dendritic cells (DCs), but directly reduces the stability of T-DC immune synapses in vitro, thus dampening T-cell activation. Overall, our results support a model in which IL4I1 increases the threshold of T-cell activation, indirectly promoting the priming of high-affinity clones while limiting memory T-cell differentiation.

scholarly journals An expanded parenchymal CD8+ T cell clone in GABA A receptor encephalitis

2020 ◽  
Vol 7 (2) ◽  
pp. 239-244 ◽  
Author(s):  
Aline Bracher ◽  
Carmen Alcalá ◽  
Jaime Ferrer ◽  
Nico Melzer ◽  
Reinhard Hohlfeld ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Gaba A ◽  
T Cell Clone

αs1-Casein-specific CD8+T Cell Clone That Inhibits Its Own Interferon-γProduction by Producing Interleukin-10

1995 ◽  
Vol 59 (12) ◽  
pp. 2274-2276 ◽  
Author(s):  
Ken-ichi Nishijima ◽  
Tatsuhiro Hisatsune ◽  
Hiroko Kato ◽  
Osamu Shiho ◽  
Shuichi Kaminogawa
Keyword(s):  
T Cell ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Interleukin 10 ◽  
T Cell Clone

scholarly journals Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion

2000 ◽  
Vol 165 (1) ◽  
pp. 96-101 ◽  
Author(s):  
Caroline Vignes ◽  
Elise Chiffoleau ◽  
Patrice Douillard ◽  
Régis Josien ◽  
Hélène Pêche ◽  
...  
Keyword(s):  
T Cell ◽  
Blood Transfusion ◽  
Cell Clone ◽  
Cd8 T Cell ◽  
Dna Vaccination ◽  
T Cell Clone

scholarly journals Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5168-5177 ◽  
Author(s):  
Cary Hsu ◽  
Stephanie A. Jones ◽  
Cyrille J. Cohen ◽  
Zhili Zheng ◽  
Keith Kerstann ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Clone ◽  
Rare Event ◽  
Cd8 T Cell ◽  
Vector System ◽  
Effector Memory ◽  
Hematopoietic Stem ◽  
Continuous Growth ◽  
T Cell Clone

Abstract Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8+ T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus–based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28−, CD45RA−, CD45RO+, and CD62L−, a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen–specific T-cell receptors, the clone secreted IFN-γ upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15Rα expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation.

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