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T Cells:Regulation and Cellular Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Cells entering the thymic phase are dividing rapidly and have the appearance of lymphoblasts. After this proliferative phase, cells take on the appearance of small resting lymphocytes and migrate through the cortex toward the medulla. Developing T cells within the thymus are called thymocytes. Several types of specialized thymic epithelial cells play critical roles in T cell development. (The histology of the thymus is described in Chapter 2.) These cells produce several thymic hormones required for thymocyte differentiation.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
TCR selection occurs in the thymic medulla where the double-positive thymocytes encounter epithelial cells expressing MHC class I and class II molecules. Only 2%–3% of the differentiating thymocytes, those that express TCR capable of interaction with MHC molecules, but tolerant to self-peptides, survive the selection process. Many newly formed thymocytes are subject to negative selection, probably as a consequence of several different sets of circumstances. Some are eliminated because the TCR is abnormal (the recombination process resulted in out-of-frame rearrangements), or because the resulting TCR is unable to interact with MHC molecules. A small percentage of double-positive thymocytes are thought to die from apoptosis because their interaction with the MHC peptide complexes is too strong (they would be activated by self-peptides). The recognition of self-peptides in the thymus is likely to involve both thymic-derived peptides and peptides of extrathymic origin. During the time T cells are differentiating, extensive development of most other tissues is taking place; hence, large numbers of cells are undergoing apoptotic death. This results in the extensive release of self-antigens, which are eventually captured by the thymic epithelial cells and presented to the pre-T cells in the context of self-MHC. The thymocytes whose TCR interact strongly with MHC-peptide complexes receive apoptotic signals and are eliminated. This negative selection process is critical to the development of self-tolerance during embryonic differentiation.
Thymus Influence on Differentiation and Functional Maturation of T Lymphocytes
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
Now, we will consider the role of thymic epithelial cell products refered to as thymic hormones in the development of T cell repertoire. The thymus can be categorized as an endocrine organ on the basis of classical criteria commonly accepted for the estimation of endocrine activity: Animals deprived of the thymus as neonates or adults represent specific defects of the immune system.Effects of thymectomy can be reversed by thymus grafting.Administration of thymus cell-free extracts can substitute, to a great extent, thymus grafting.Purified and well-characterized thymic extracts or synthesized products are functionally similar to crude thymic preparations.Thymic-characteristic biological activity is detected in circulating blood.Serum thymic-born activity disappears after thymectomy and may be reconstituted by thymus grafting or by parenteral administration of thymic extracts.91
An update on thymectomy in myasthenia gravis
Published in Expert Review of Neurotherapeutics, 2019
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].
Interactions between thymic endothelial cells and thymocytes are influenced by growth hormone
Published in Growth Factors, 2020
Marvin Paulo Lins, Iana Mayane Mendes Nicácio Viana, Salete Smaniotto, Maria Danielma dos Santos Reis
Although the mechanisms that drive thymocyte migration are not yet fully understood, clear evidences have shown that the cells of the thymic microenvironment (mainly thymic epithelial cells) influence the development of T cells through cell surface molecules, such as Delta-like canonical Notch ligand 4, Kit ligand, major histocompatibility complex (MHC) proteins, and integrins. In addition, extracellular matrix (ECM) elements, such as collagen, fibronectin (FN), and laminin (LM), are involved in interactions between thymocytes and stromal cells. Furthermore, thymic cells (both lymphoid and non-lymphoid) are sensitive to endogenous and exogenous factors, such as hormones, neurotransmitters, cytokines, and growth factors (Pérez et al. 2019; Savino et al. 2015).
Cellular mechanisms and clinical applications for phenocopies of inborn errors of immunity: infectious susceptibility due to cytokine autoantibodies
Published in Expert Review of Clinical Immunology, 2023
Rui Sun, Yating Wang, Hassan Abolhassani
Auto-Abs against IL-17A/F (aAb-IL-17) and/or IL-22 (aAb-IL-22) can be classified in two situations to discuss: Unknown genetic reason with aAb-IL-17/22; and aAb-IL-17/22 due to AIRE mutations. So far, there are no specific HLA II alleles/T and B cell epitopes reported with aAb-IL-17/22 production. In most published studies, the incomplete penetrant association between aAb-IL-17/22, CMC, and APECED has been shown. The correlation between the presence of aAb-IL-17/22 and CMC is ~70%. The correlation between APECED and CMC is more than 80% [98]. And more than 90% of reported APECED patients carried aAb-IL-17/22 [99]. APECED has a higher prevalence in a specific population, such as Finnish (>80% with p.R257×), Sardinians (>90% with p.R139×), and Iranian Jews (with unique variant p.Y85C) with incidences of ∼1/25000, ∼1/14500, and ∼1/9000, respectively [100–103]. Certain types of autoAbs and CMC clinical manifestation can be observed in unique AIRE mutations, including p.R257× (CMC+, aAb-IL-22+, aAb-IL-17F+), p.G228W (aAb-type I IFNs+, aAb-IL-22-, aAb-IL-17F-), c.967_979del13 (CMC+, aAb-IL-22+, aAb-IL-17F+) and c.1064–1068dupCCCGG (extremely high titer of aAb-IL-22) [104]. Also, in the patients with thymoma aAb-IL-17/22 and CMC infectious manifestation can be observed [105]. Both primary (AIRE genetic mutation) and secondary (thymoma) defects correlated with abnormal autoAbs production indicate the hypothesis of central T-cell tolerance impairment: such as autoreactive T cell escape deletion, mTECs (medullary thymic epithelial cells) antigen presentation failure, negative selection failure, and unbalanced Treg cells differentiation [106] (Table 1).