Engineering approaches for regeneration of T lymphopoiesis

Roh, Kyung-Ho; Roy, Krishnendu

doi:10.1186/s40824-016-0067-1

Cited by 12 publications

(14 citation statements)

References 87 publications

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“…Thus novel approaches are needed to stably expand and maintain the responsiveness and functions of Vγ9Vδ2 T cells. Since our data strongly indicate that Vγ9Vδ2 T cells within the blood circulation of adults are derived post-natally, strategies could be developed to enhance de novo generation of Vγ9Vδ2 T cells in cancer patients (55,56). (bottom) repertoire.…”

Section: Discussionmentioning

confidence: 99%

TCR Sequencing Reveals the Distinct Development of Fetal and Adult Human Vγ9Vδ2 T Cells

Papadopoulou

Tieppo

McGovern

et al. 2019

The Journal of Immunology

117

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Phosphoantigen-reactive Vγ9Vδ2 T cells represent the main innate human γδ T cell subset and dominate the fetal and adult peripheral blood γδ T cell repertoire. It has been hypothesized that adult blood Vγ9Vδ2 T cells find their origin in the fetus like it is established for mouse innate γδ T cells. In order to address this issue, we analyzed the complementarity-determining-region-3 (CDR3) of the T cell receptor (TCR) of human blood and thymic Vγ9Vδ2 T cells from fetal until adult life. We first identified key differences in the CDR3 repertoire of fetal and adult blood Vγ9Vδ2 T cells, including in CDR3 features important for phosphoantigen-reactivity. Next, we showed that most of these key adult CDR3 features were already present in the postnatal thymus and were further enhanced upon selection in vitro by the microbial-derived phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP). Finally, we demonstrated that the generation of a fetal-type or adult-type Vγ9Vδ2 CDR3 repertoire is determined by the fetal and post-natal nature of the hematopoietic-stemand-precursor-cell (HSPC). Thus, our data indicate that fetal blood Vγ9Vδ2 T cells find their origin in the fetal thymus while adult blood Vγ9Vδ2 T cells are generated to a large degree independently after birth.

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Section: Discussionmentioning

confidence: 99%

TCR Sequencing Reveals the Distinct Development of Fetal and Adult Human Vγ9Vδ2 T Cells

Papadopoulou

Tieppo

McGovern

et al. 2019

The Journal of Immunology

117

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“…Applying the synthetic biology approach, Wendell Lim’s group recently demonstrated versatile functionalities and activation states that engineered T cells have by taking advantage of specific transcriptional responses induced by customized synthetic Notch receptor/ligand interactions [92]. Additionally, efforts in engineering immunity via engineering the microenvironment using scaffolds [93,94] or organoid culture [95,96] have paved the way of applying in vitro engineered immune cells for therapeutics. With continued development of high-throughput technology and synthetic biology tools, immune engineering will be a critical link between basic immunology discoveries and their application.…”

Section: From Systems Immunology To Engineering Immunitymentioning

confidence: 99%

Immune engineering: From systems immunology to engineering immunity

Jiang

2017

Current Opinion in Biomedical Engineering

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The smallpox vaccine represents the earliest attempt in engineering immunity. The recent success of chimeric antigen receptor T cells (CAR-T cells) in cancer once again demonstrates the clinical potential of immune engineering. Inspired by this success, diverse approaches have been used to boost various aspects of immunity: engineering dendritic cells (DCs), natural killer (NK) cells, T cells, antibodies, cytokines, small peptides, and others. With recent development of various high-throughput technologies (of which engineers, especially biomedical engineers/bioengineers contributed significantly), such as immune repertoire sequencing, and analytical methods, a systems level of understanding immunity (or the lack of it) beyond model animals has provided critical insights into the human immune system. This review focuses on recent progressed made in systems biology and the engineering of adaptive immunity.

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“…As a result, there have been many experimental attempts to mimic the thymic niche in order to generate T cells in vitro (reviewed in [14, 15]). This has resulted in several different protocols that provide a 2D and 3D structural environment to support T cell differentiation (Box 1).…”

Section: Approaches For Generating T Cellsmentioning

confidence: 99%

T Cell Genesis: In Vitro Veritas Est ?

Brauer

Singh

Xhiku

et al. 2016

Trends in Immunology

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T cells, as orchestrators of the adaptive immune response, serve important physiological and potentially therapeutic roles, for example in cancer immunotherapy. T cells are readily isolated from patients; however, the yield of antigen-specific T cells is limited, thus making their clinical use challenging. Therefore, the generation of T lymphocytes from hematopoietic stem/progenitor cells (HSPCs) and human pluripotent stem cells (PSCs) in vitro provides an attractive method for large-scale production and genetic manipulation of T cells. In this review, we discuss recent strategies for the generation of T cells from human HSPCs and PSCs in vitro. Continued advancement in the generation of human T cells in vitro will expand their benefits and therapeutic potential in the clinic.

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Engineering approaches for regeneration of T lymphopoiesis

Cited by 12 publications

References 87 publications

TCR Sequencing Reveals the Distinct Development of Fetal and Adult Human Vγ9Vδ2 T Cells

TCR Sequencing Reveals the Distinct Development of Fetal and Adult Human Vγ9Vδ2 T Cells

Immune engineering: From systems immunology to engineering immunity

T Cell Genesis: In Vitro Veritas Est ?

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