Making Thymus Visible: Understanding T-Cell Development from a New Perspective

Abstract

T-cell development is coupled with a highly ordered migratory pattern. Lymphoid progenitors must follow a precise journey; starting from the hematopoietic tissue, they move toward the thymus and then migrate into and out of distinct thymic microenvironments, where they receive signals and cues required for their differentiation into naïve T-cells. Knowing where, when, and how these cells make directional “decisions” is key to understanding T-cell development. Such insights can be gained by directly observing developing T-cells within their environment under various conditions and following specific experimental manipulations. In the last decade, several model systems have been developed to address temporal and spatial aspects of T-cell development using imaging approaches. In this perspective article, we discuss the advantages and limitations of these systems and highlight a particularly powerful in vivo model that has been recently established. This model system enables the migratory behavior of all thymocytes to be studied simultaneously in a noninvasive and quantitative manner, making it possible to perform systems-level studies that reveal fundamental principles governing T-cell dynamics during development and in disease.

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

“…Zebrafish may prove a useful model for addressing this question. The developmental origin, anatomical location and genetics underlying the development of adaptive immunity are largely conserved between zebrafish and mammals [241][242][243][244][245][246]. In recent years, studies of zebrafish lymphocytes have also revealed the existence of functionally conserved mature T cell subsets, such as CD4 + helper T cells [247,248], T regulatory cells [247,249,250] and γδ T cells [251].…”

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…To prevent the kidney from returning to its original position, improved methods suggest closing the lateral sides of the skin incision with stitches (Caetano et al, 2012). Although the transplanted thymus approach has been successfully used in various studies, limitations of this approach include the complexity of the surgery required for transplantation, and the fact that different corporal conditions exist in the surrounding environment of a thymus transplanted in the kidney as opposed to a thymus located in the thoracic cavity (Aghaallaei & Bajoghli, 2018). Ex vivo alternatives to the complex transplantation procedure include extraction of individual thymic lobes perfused with oxygenated medium, followed by imaging by two photon microscopy , and imaging thymic slices Pérez et al, 2007;Savino et al, 1989), Plasmodium spp., Francelin et al, 2011;Gameiro et al, 2010) and T. gondii (Huldt et al 1973;Kugler et al, 2016;…”

Off the beaten track: defining the developmental path of T cells through the human thymus

“…T cell development starts when T cell precursors migrate from the bone marrow or the fetal liver to the thymus. 1 In the thymic microenvironment, these precursor cells undergo a series of differentiation and selection events in different regions of the thymus, resulting in a diverse repertoire of mature T cells to establish immune protection against foreign antigens and immune tolerance toward self-antigens. 2 This process happens prenatally and involves several cell types including thymic epithelial cells and dendritic cells (DCs).…”

“…2 This process happens prenatally and involves several cell types including thymic epithelial cells and dendritic cells (DCs). 1 Recent development of single-cell RNA seq (scRNA-seq) technology has allowed precise mapping of different cell types and trajectories of organ development. 3 Indeed, single-cell RNA sequencing (scRNA-seq) has revealed details of murine T cell development and thymic composition 4 ; however, human T cell development is vastly distinct from other animals.…”

“…In order to accommodate to hypoxic conditions, where mitochondrial oxidative phosphorylation is disrupted, HIF-1 upregulates genes related to glucose uptake and glycolysis. 1…”