Dynamics of Immunoglobulin and T-cell Receptor Genes Recombinations During Lymphocyte Development
Gérard Chaouat in The Immunology of the Fetus, 2020
T-cell maturation occurs in the thymus, where distinct subpopulations of thymocytes of various developmental stages reside. At least four such subpopulations of mouse thymocytes can be defined by virtue of their T-cell markers. Thus, immunocompetent (medullary) thymocytes, like peripheral cells, express either Lyt.2 or L3T4 antigens but not both; whereas, nonfunctional (cortical) thymocytes express both markers. In addition, about 2 to 3% of thymic cells are negative for Lyt.2 and L3T4 expression.21,22 However, these latter double-negative cells constitute the vast majority of thymocytes before day 17 of fetal life, but decrease during subsequent development.40,41 Double negative thymocytes have been previously shown to express high levels of TcRβ and TCRγ, but little, if any, TcRa mRNA.39 Recent evidence suggests that these cells express a novel heterodimeric receptor encoded by the γ chain and another unidentified polypeptide in both mice and humans.19,20
Systems IntegrationPsychoneuroimmunology
Len Wisneski in The Scientific Basis of Integrative Health, 2017
Thymic hormones regulate IL-2 production, which then aids in the maturation of thymocytes and the presence of IL-2 receptors on mature T cells. This effect appears to be synergistic with IL-1 (Hadden et al., 1991). In addition, numerous hormones produced within the thymus are classically thought of as pituitary hormones (e.g., GH, prolactin, ACTH, luteinizing hormone [LH], and others). I cannot emphasize enough the importance of such findings. It has forced us to alter our whole concept of how the body functions. These thymic hormones have paracrine–autocrine actions, which serve to regulate immune action and influence neuroendocrine functions that affect the regulation of the HPA axis (Savino et al., 1998). Glucocorticoids play a particularly interesting role in T-lymphocyte development. At high concentrations, they induce thymocyte apoptosis, but at lower concentrations, they actually potentiate thymocyte maturation (Vacchio et al., 1998). We will come back to this point when we look at the role that glucocorticoids play in stress (see Chapter 3, which covers the stress system).
Relation between Lymphatic and Immune Systems and their Role in Homeostasis
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein in Immunoregulatory Role of Thymus, 2019
Using a panel of monoclonal antibodies to T cell surface antigens, Reinherz and Schlossman52 in 1980 were able to determine the distribution of T cell antigens series at different stages of T lymphocyte ontogeny. Immature thymocytes located in the thymic cortex express T9 and T10 antigens, (stage I of intrathymic maturation). The T9 antigen composed of two glycosylated polypeptides (90 kDa each) has been identified as the transferrin receptor.53 After the loss of T9, intermediate thymocyte, stage II, express TIO, T6 cluster of differentiation (CD) 1, T4 (CD4), T5/8 (CD8), and T1 (CD5). T6 (CD1), the human analog of the mouse TL antigen, formerly described as HTL antigen, and T10 antigens are expressed only during intrathymic differentiation of T cells. Unlike the T6 (CD1), which is present only on intermediate thymocytes, the T10 antigen marks all the three stages of thymocyte differentiation. All mature thymocytes, stage III, carry T10, T1 (CD5), and T3 (CD3) antigens and differ in respect to the presence of T4 (CD4) or T8 (CD8) molecules. This is also the main difference between two functionally distinct broad categories of peripheral T lymphocytes with respective phenotypes of CD3, CD5 and CD4, or CD3, CD5, and CD8. In common with thymocytes, they additionally possess CD2 (E-rosette receptor), CD25 (Tac or IL-2 receptor), and clonally distributed Ti antigenic receptor.
Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice
Published in Journal of Immunotoxicology, 2018
Lucie Leung-Gurung, Priscilla Escalante Cobb, Faraj Mourad, Cristina Zambrano, Zachary Muscato, Victoria Sanchez, Kanya Godde, Christine Broussard
T-Cell receptor expression levels reflect thymocyte maturational stage. Thymocytes that express no or low levels of TCR are immature; those with high levels are more mature. Following the above treatments, the isolated cells underwent labeling with a cocktail containing the following antibodies (all BioLegend, San Diego, CA, USA) that had been titrated for use to stain freshly isolated and cultured thymocytes. The antibodies used included APC-anti-CD4 (clone RM4-5, rat IgG2a), FITC-anti-CD8 (clone 53-6.7, rat IgG2a), PE-anti-CD5 (clone 53-7.3, rat IgG2a), PE/Cy5-anti-TCR (clone H57–597, Armenian hamster IgG). In brief, the isolated cells were stained with fluorochrome-conjugated antibodies for 30 min in the dark on ice, then washed with phosphate-buffered saline (PBS, pH 7.4) containing 1% FBS. Thereafter, the cells were immediately collected on the Accuri C6 system and analyzed. In each case, a minimum of 10 000 events/sample was acquired, and levels of marker expression (and hence, population dynamics/status) determined for each treatment group.
An update on thymectomy in myasthenia gravis
Published in Expert Review of Neurotherapeutics, 2019
Amelia Evoli, Elisa Meacci
The thymus is the organ where T cell repertoire and central tolerance are established. Developing T cells (thymocytes) mature from hematological precursors, through cross-talk with thymic epithelial cells (TECs), macrophages and dendritic cells, in their passage across cortical and medullary thymic compartments. In the cortex, only thymocytes recognizing major histocompatibility complex (MHC) class II-bound endogenous peptides survive (positive selection). In the medulla, TECs and dendritic cells express tissue specific antigens (TSAs) and present them to thymocytes. T cells that recognize self-antigens with high affinity are deleted from the thymus (negative selection). Through this process (thymopoiesis), the thymus produces and exports functional naïve T lymphocytes to the periphery. The autoimmune regulator (AIRE) protein has a crucial role in T cell selection as it controls TSA transcription in the thymic medulla [10]. In addition, the thymus contributes to tolerance through production of T regulatory (Treg) cells, which suppress conventional T cell proliferation [11].
Growth hormone enhances the CD34+ stem cells repopulation of the male albino rat thymus gland in cyclophosphamide induced injury: immunohistochemical and electron microscopic study
Published in Ultrastructural Pathology, 2023
Amira I. Shrief, Walaa H.E. Hamed, Shireen A Mazroa, Amal M. Moustafa
Examination of the sections in the thymus gland of all subgroups of control rats (group І) revealed the same structure. The thymus gland was covered with a thin connective tissue capsule and was subdivided into intercommunicating lobules by thin connective tissue septa. Each lobule was divided into outer darkly stained cortex and inner pale medulla with a clear demarcation between them (Figure 1a). The thymic cortex was populated mainly by large number of closely packed thymoblasts and fewer epithelial reticular cells (ERCs). Thymoblasts had large rounded nuclei. The ERCs had oval to round pale stained nuclei. Macrophages and blood capillaries were also seen (Figure 1b). The thymic medulla was formed of loosely packed thymocytes with small rounded deeply stained nuclei, more prominent ERCs and few Hassall’s corpuscles. Hassall’s corpuscles were formed of a central hyaline acidophilic mass surrounded with one layer of ERCs (Figure 1c).